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FGF23 (UniProt accession Q9GZV9) encodes fibroblast growth factor 23, a bone-derived endocrine hormone that functions as the principal phosphaturic regulator of mineral homeostasis in humans (agoro2023regulationoffgf23 pages 3-4, edmonston2024fgf23andklotho pages 2-4). The protein belongs to the heparin-binding growth factors family and contains characteristic FGF domains (IPR002209, IPR008996), confirming the identity matches the provided UniProt annotation.
FGF23 is synthesized as a 251-amino-acid precursor protein that, following signal peptide cleavage, yields a secreted 227-amino-acid glycoprotein with an approximate molecular mass of 32 kDa (agoro2023regulationoffgf23 pages 1-2, dastghaib2023newconceptsin pages 2-4). The intact, biologically active form (iFGF23) can be proteolytically processed at the R176HTR179↓S180AE motif by a furin-like proprotein convertase, generating an N-terminal fragment (~20 kDa) and a C-terminal fragment (~12 kDa) (agoro2023regulationoffgf23 pages 1-2, portalescastillo2022pthfgf23klotho pages 3-5).
Post-translational modifications critically regulate FGF23 bioactivity. GALNT3-mediated O-glycosylation—particularly at threonine 178 following prior glycosylation at threonine 171—protects the intact hormone from proteolytic cleavage and thereby increases circulating bioactive FGF23 (agoro2023regulationoffgf23 pages 1-2, agoro2023regulationoffgf23 pages 3-4). Conversely, FAM20C phosphorylates serine 180, which inhibits GALNT3 activity and promotes furin-mediated cleavage into inactive fragments (agoro2023regulationoffgf23 pages 1-2, portalescastillo2022pthfgf23klotho pages 3-5). This dynamic balance between glycosylation-mediated stabilization and phosphorylation-promoted cleavage determines the proportion of circulating intact hormone versus fragments. Mutations at arginine 176 or 179 that prevent cleavage cause accumulation of intact FGF23 and lead to autosomal-dominant hypophosphatemic rickets (agoro2023regulationoffgf23 pages 1-2, portalescastillo2022pthfgf23klotho pages 3-5).
FGF23 is produced primarily by osteocytes and osteoblast-lineage cells within bone tissue, which serve as the main endocrine source (agoro2023regulationoffgf23 pages 1-2, dastghaib2023newconceptsin pages 1-2, agoro2023regulationoffgf23 pages 3-4). These bone cells detect circulating metabolites, hormones, and minerals—particularly phosphate and calcium—and regulate FGF23 production accordingly through transcriptional, post-translational, and proteolytic mechanisms (agoro2023regulationoffgf23 pages 1-2, agoro2023regulationoffgf23 pages 2-3). Under specific physiological or pathological conditions, bone marrow stromal cells and erythroid cells can contribute to FGF23 production, particularly during anemia or in response to elevated erythropoietin (agoro2023regulationoffgf23 pages 1-2).
The kidney represents the principal endocrine target organ where FGF23 exerts its canonical effects on mineral metabolism (latic2022interactionofvitamin pages 5-7, agoro2023regulationoffgf23 pages 3-4, latic2022interactionofvitamin pages 7-8). Within the kidney, FGF23 acts on both proximal and distal renal tubules through basolateral FGFR–α-Klotho receptor complexes. In the proximal tubule, FGF23 regulates phosphate reabsorption and vitamin D metabolism; in the distal tubule, it can modulate calcium and sodium reabsorption through TRPV5 and NCC channels, respectively (latic2022interactionofvitamin pages 5-7, latic2022interactionofvitamin pages 7-8).
The parathyroid glands represent another important physiological target tissue, where FGF23 can suppress parathyroid hormone (PTH) gene expression and secretion (dastghaib2023newconceptsin pages 1-2, martinezheredia2024nonclassicaleffectsof pages 2-4). Additional target tissues include bone itself, where FGF23 may exert local autocrine or paracrine effects on osteoblast activity and bone remodeling, although these effects are complex and context-dependent (martinezheredia2024nonclassicaleffectsof pages 2-4, martinezheredia2024nonclassicaleffectsof pages 4-5). Under pathological conditions—particularly in chronic kidney disease (CKD) with markedly elevated FGF23 levels—the heart becomes a significant target organ, with effects on cardiomyocytes and cardiac fibroblasts contributing to cardiovascular remodeling (diazhaaz2025effectsoffibroblast pages 4-5, edmonston2024fgf23andklotho pages 5-6).
FGF23 functions as a hormone rather than an enzyme, and therefore has no catalytic substrate or enzymatic activity. Its primary molecular function is to serve as a signaling ligand that binds to fibroblast growth factor receptors (FGFRs) in obligate association with the transmembrane co-receptor α-Klotho (edmonston2024fgf23andklotho pages 2-4, dastghaib2023newconceptsin pages 1-2).
The functional receptor complex consists of FGF23 bound to specific FGFR isoforms together with α-Klotho. Structural and biochemical studies have identified FGFR1c, FGFR3c, and FGFR4 as the principal receptor isoforms involved in FGF23 signaling (edmonston2024fgf23andklotho pages 2-4, chen2023structuralbasisfor pages 1-2). High-resolution cryo-electron microscopy structures reveal that FGF23's N-terminal region engages the FGFR, while its C-terminal tail interacts with α-Klotho (edmonston2024fgf23andklotho pages 2-4, chen2023structuralbasisfor pages 2-3). α-Klotho functions as a molecular scaffold that stabilizes the FGF23–FGFR complex, converting a canonical FGF receptor into a high-affinity FGF23-specific receptor (edmonston2024fgf23andklotho pages 2-4, chen2023structuralbasisfor pages 1-2).
Recent structural studies reveal an asymmetric 1:2:1:1 stoichiometry for the active signaling complex: FGF23–FGFR–α-Klotho–heparan sulfate (chen2023structuralbasisfor pages 2-3, chen2023structuralbasisfor pages 1-2). In this model, a single heparan sulfate chain enables the primary 1:1:1 FGF23–FGFR–α-Klotho ternary complex to recruit a second FGFR molecule, leading to asymmetric receptor dimerization that is mandatory for tyrosine kinase activation and downstream signaling (chen2023structuralbasisfor pages 2-3, chen2023structuralbasisfor pages 6-7). Notably, α-Klotho does not directly recruit the secondary receptor but rather stabilizes the primary complex, allowing heparan sulfate to mediate receptor dimerization (chen2023structuralbasisfor pages 1-2, chen2023structuralbasisfor pages 6-7).
Upon receptor binding, FGF23 activates FGFR substrate 2α (FRS2α) and downstream RAS–mitogen-activated protein kinase (MAPK) signaling, including ERK1 and ERK2 (edmonston2024fgf23andklotho pages 2-4, agoro2023regulationoffgf23 pages 3-4, latic2022interactionofvitamin pages 7-8). In renal proximal tubules, MAPK signaling through ERK1/2 leads to activation of early growth response protein 1 (EGR1) and serum/glucocorticoid-regulated kinase 1 (SGK1), which mediate effects on phosphate transporters and contribute to phosphaturia (agoro2023regulationoffgf23 pages 2-3, latic2022interactionofvitamin pages 14-15).
Under pathological conditions characterized by extremely high FGF23 concentrations and α-Klotho deficiency—such as advanced CKD—FGF23 can activate FGFR4 in cardiac tissue independently of α-Klotho (prudhomme2024antiinflammatoryroleof pages 3-5, diazhaaz2025effectsoffibroblast pages 4-5, edmonston2024fgf23andklotho pages 5-6). This klotho-independent pathway involves FGFR4-mediated recruitment and phosphorylation of phospholipase Cγ (PLCγ), which activates the calcineurin/nuclear factor of activated T-cells (NFAT) signaling cascade associated with pathological cardiac hypertrophy and remodeling (diazhaaz2025effectsoffibroblast pages 4-5, nakano2023directandindirect pages 2-3).
FGF23's primary physiological role is to function as a phosphaturic hormone that promotes urinary phosphate excretion and lowers serum phosphate concentrations (agoro2023regulationoffgf23 pages 3-4, edmonston2024fgf23andklotho pages 2-4). In the renal proximal tubule, FGF23 signaling through FGFR1–α-Klotho complexes and downstream MAPK activation promotes the internalization and degradation of apical membrane sodium-phosphate cotransporters, specifically NPT2a (NaPi-IIa, encoded by SLC34A1) and NPT2c (NaPi-IIc, encoded by SLC34A3) (portalescastillo2022pthfgf23klotho pages 3-5, agoro2023regulationoffgf23 pages 3-4, agoro2023regulationoffgf23 pages 2-3). The removal of these transporters from the brush border membrane decreases filtered phosphate reabsorption from tubular fluid, thereby increasing urinary phosphate excretion and reducing serum phosphate levels (agoro2023regulationoffgf23 pages 3-4, agoro2023regulationoffgf23 pages 7-8).
FGF23 exerts profound effects on vitamin D metabolism by regulating the expression of key vitamin D-metabolizing enzymes in the kidney (agoro2023regulationoffgf23 pages 3-4, latic2022interactionofvitamin pages 7-8, latic2022interactionofvitamin pages 5-7). FGF23 suppresses transcription of CYP27B1, the enzyme responsible for 1α-hydroxylation that converts 25-hydroxyvitamin D into the active metabolite 1,25-dihydroxyvitamin D (calcitriol) (agoro2023regulationoffgf23 pages 3-4, latic2022interactionofvitamin pages 7-8, latic2022interactionofvitamin pages 2-4). Simultaneously, FGF23 increases transcription of CYP24A1, the 24-hydroxylase enzyme that promotes vitamin D catabolism and inactivation (agoro2023regulationoffgf23 pages 3-4, latic2022interactionofvitamin pages 7-8, latic2022interactionofvitamin pages 2-4). Through these reciprocal effects—suppressing synthesis while enhancing degradation—FGF23 reduces circulating concentrations of active vitamin D (latic2022interactionofvitamin pages 7-8, martinezheredia2024nonclassicaleffectsof pages 1-2).
This regulation forms a critical negative feedback loop: circulating 1,25-dihydroxyvitamin D stimulates FGF23 transcription in bone through vitamin D receptor-dependent mechanisms, while FGF23 acts on the kidney to limit active vitamin D production (agoro2023regulationoffgf23 pages 3-4, latic2022interactionofvitamin pages 5-7, portalescastillo2022pthfgf23klotho pages 5-7). Lower calcitriol levels indirectly reduce intestinal phosphate and calcium absorption, complementing FGF23's direct renal phosphaturic effect and contributing to overall phosphate homeostasis (portalescastillo2022pthfgf23klotho pages 3-5, latic2022interactionofvitamin pages 5-7).
FGF23 participates in a complex regulatory network with parathyroid hormone (PTH) and vitamin D. Under physiological conditions, FGF23 can suppress PTH secretion from parathyroid cells through both α-Klotho-dependent ERK1/2 signaling and proposed klotho-independent calcineurin-dependent pathways (martinezheredia2024nonclassicaleffectsof pages 2-4). However, in advanced CKD, prolonged exposure to high FGF23 levels downregulates parathyroid α-Klotho and FGFR1c expression, producing FGF23 resistance (martinezheredia2024nonclassicaleffectsof pages 2-4). Combined with FGF23-mediated suppression of calcitriol and consequent hypocalcemia, this resistance contributes to the development of secondary hyperparathyroidism in CKD (martinezheredia2024nonclassicaleffectsof pages 2-4, edmonston2024fgf23andklotho pages 4-5).
The production and secretion of bioactive FGF23 is regulated at multiple levels through transcriptional induction, post-translational modification, and proteolytic processing (agoro2023regulationoffgf23 pages 1-2, vervloet2022sheddinglighton pages 10-11). A comprehensive summary of regulatory factors is provided in the table below.
| Regulatory factor | Effect on FGF23 | Mechanism | Citations |
|---|---|---|---|
| Phosphate | Increases intact FGF23 | Osteocyte phosphate sensing involves PiT2 and ligand-independent FGFR1 signaling. Phosphate also increases GALNT3, promoting protective O-glycosylation and reducing intracellular cleavage of FGF23. | (vervloet2022sheddinglighton pages 2-4, vervloet2022sheddinglighton pages 1-2, agoro2023regulationoffgf23 pages 2-3) |
| Calcium | Increases FGF23; permits the phosphate response | Calcium can stimulate FGF23 transcription and may be required for phosphate- or PTH-induced increases. Calcium–phosphate calciprotein particles can also stimulate osteocyte FGF23 expression and secretion. | (vervloet2022sheddinglighton pages 2-4, agoro2023regulationoffgf23 pages 2-3) |
| 1,25-dihydroxyvitamin D (calcitriol) | Increases FGF23 | Activates vitamin-D-receptor-dependent transcription in osteoblast-lineage cells, forming a feedback loop in which FGF23 subsequently suppresses renal calcitriol synthesis. Phosphate may enhance this transcriptional response. | (agoro2023regulationoffgf23 pages 3-4, vervloet2022sheddinglighton pages 4-6, agoro2023regulationoffgf23 pages 4-5) |
| Parathyroid hormone (PTH) | Generally increases FGF23 chronically; acute effects can be biphasic | Signals through PTH1R and Nurr1 and suppresses sclerostin, thereby activating Wnt-associated FGF23 expression. Acute PTH can lower intact FGF23 through phosphaturia or increased cleavage, whereas sustained exposure generally increases production. | (vervloet2022sheddinglighton pages 10-11, vervloet2022sheddinglighton pages 4-6, agoro2023regulationoffgf23 pages 4-5) |
| GALNT3 (GalNAc-T3) | Increases intact, bioactive FGF23 | O-glycosylates FGF23—especially Thr178 after modification at Thr171—protecting the furin-recognition region from cleavage and stabilizing the full-length hormone. | (agoro2023regulationoffgf23 pages 1-2, agoro2023regulationoffgf23 pages 3-4) |
| FAM20C | Decreases intact FGF23; increases cleavage fragments | Phosphorylates Ser180, antagonizing GALNT3-mediated glycosylation and permitting furin-like proteolysis into N- and C-terminal fragments. | (agoro2023regulationoffgf23 pages 1-2, portalescastillo2022pthfgf23klotho pages 3-5) |
| Erythropoietin (EPO) | Increases FGF23 production, often with increased cleavage | Kidney-derived or therapeutic EPO stimulates FGF23 production in osteoblast/osteocyte-lineage and erythroid or marrow stromal cells, particularly during anemia and hypoxia. | (agoro2023regulationoffgf23 pages 1-2, agoro2023regulationoffgf23 pages 3-4) |
| Lipocalin-2 (LCN2) | Increases FGF23 | In CKD, renal EGF–EGFR–HIF1α signaling induces LCN2; circulating LCN2 then activates osteocyte LCN2R–cAMP–PKA–CREB signaling to stimulate FGF23 transcription. | (agoro2023regulationoffgf23 pages 4-5, agoro2023regulationoffgf23 pages 3-4) |
| PHEX | Decreases FGF23 | Acts locally in bone with DMP1 to restrain FGF23 expression and may facilitate its cleavage. Loss-of-function causes excess intact FGF23, renal phosphate wasting, and hypophosphatemia. | (vervloet2022sheddinglighton pages 10-11, vervloet2022sheddinglighton pages 4-6) |
| DMP1 | Decreases FGF23 | Osteocyte-derived matrix protein that suppresses FGF23 through a local pathway shared with PHEX. DMP1 deficiency—or its suppression in CKD—derepresses FGF23 production. | (vervloet2022sheddinglighton pages 10-11, vervloet2022sheddinglighton pages 4-6) |
Table: Major mineral, endocrine, post-translational, kidney-derived, and bone-local regulatory factors governing FGF23 transcription, processing, and bioactive hormone abundance.
Elevated serum phosphate represents a major stimulus for FGF23 production (vervloet2022sheddinglighton pages 2-4, vervloet2022sheddinglighton pages 1-2, agoro2023regulationoffgf23 pages 2-3). Osteocyte phosphate sensing involves the sodium-phosphate cotransporter PiT2 and ligand-independent FGFR1 signaling (agoro2023regulationoffgf23 pages 2-3). Phosphate also increases GALNT3 expression, promoting protective O-glycosylation that stabilizes intact FGF23 and reduces its intracellular cleavage (vervloet2022sheddinglighton pages 2-4, vervloet2022sheddinglighton pages 1-2).
Calcium can directly stimulate FGF23 transcription and appears necessary for phosphate- or PTH-induced FGF23 increases (vervloet2022sheddinglighton pages 2-4, agoro2023regulationoffgf23 pages 2-3). Calcium-phosphate-protein complexes known as calciprotein particles (CPPs) can stimulate osteocyte FGF23 expression and secretion, potentially contributing to elevated FGF23 in CKD (vervloet2022sheddinglighton pages 2-4, agoro2023regulationoffgf23 pages 2-3).
Active vitamin D (1,25-dihydroxyvitamin D/calcitriol) strongly induces FGF23 transcription in osteoblast-lineage cells through vitamin D receptor-dependent mechanisms (agoro2023regulationoffgf23 pages 3-4, vervloet2022sheddinglighton pages 4-6, agoro2023regulationoffgf23 pages 4-5). This creates the negative feedback loop wherein FGF23 subsequently suppresses renal calcitriol synthesis.
Parathyroid hormone generally increases FGF23 during sustained exposure, signaling through PTH1R and the intracellular mediator Nurr1, and also by suppressing sclerostin to activate Wnt-associated FGF23 expression (vervloet2022sheddinglighton pages 10-11, vervloet2022sheddinglighton pages 4-6, agoro2023regulationoffgf23 pages 4-5). However, acute PTH effects can be biphasic, sometimes lowering intact FGF23 through phosphaturia or increased cleavage (vervloet2022sheddinglighton pages 10-11, agoro2023regulationoffgf23 pages 4-5).
In CKD and acute kidney injury, several kidney-derived factors stimulate bone FGF23 production (agoro2023regulationoffgf23 pages 1-2, agoro2023regulationoffgf23 pages 4-5, agoro2023regulationoffgf23 pages 3-4). Erythropoietin (EPO) induces FGF23 in osteoblast/osteocyte-lineage and erythroid cells, particularly during anemia (agoro2023regulationoffgf23 pages 1-2). In CKD, renal EGF–EGFR–HIF1α signaling induces lipocalin-2 (LCN2), which then activates osteocyte LCN2R–cAMP–PKA–CREB signaling to stimulate FGF23 transcription (agoro2023regulationoffgf23 pages 4-5, agoro2023regulationoffgf23 pages 3-4). Additionally, glycerol-3-phosphate is converted to lysophosphatidic acid (LPA), which activates LPAR1 signaling in bone to promote FGF23 production (agoro2023regulationoffgf23 pages 4-5, agoro2023regulationoffgf23 pages 3-4).
PHEX and DMP1 are local bone-derived proteins that normally restrain osteocytic FGF23 expression (vervloet2022sheddinglighton pages 10-11, vervloet2022sheddinglighton pages 4-6). Loss-of-function mutations in either gene cause excessive intact FGF23 production, resulting in renal phosphate wasting and hypophosphatemia characteristic of X-linked hypophosphatemia (PHEX deficiency) or autosomal recessive hypophosphatemic rickets (DMP1 deficiency) (vervloet2022sheddinglighton pages 10-11, vervloet2022sheddinglighton pages 4-6). In CKD, uremia can suppress osteocyte DMP1 expression, contributing to increased FGF23 production (vervloet2022sheddinglighton pages 4-6).
A comprehensive summary of FGF23's molecular mechanisms, signaling pathways, and physiological effects is provided in the table below.
| Aspect | Details | Key Citations |
|---|---|---|
| Protein structure and processing | Human FGF23 is synthesized as a 251-amino-acid precursor; signal-peptide removal yields the secreted, biologically active 227-amino-acid glycoprotein of approximately 32 kDa. A furin-like convertase cleaves the R176–H177–T178–R179↓S180 motif to generate approximately 20-kDa N-terminal and 12-kDa C-terminal fragments. | (agoro2023regulationoffgf23 pages 1-2, dastghaib2023newconceptsin pages 2-4, portalescastillo2022pthfgf23klotho pages 3-5) |
| Post-translational control | GALNT3-mediated O-glycosylation—particularly at Thr178 after modification of Thr171—protects FGF23 from convertase cleavage and preserves intact hormone. FAM20C phosphorylation of Ser180 opposes this glycosylation and favors cleavage. Cleavage-resistant substitutions at Arg176 or Arg179 cause accumulation of intact FGF23 in autosomal-dominant hypophosphataemic rickets. | (agoro2023regulationoffgf23 pages 1-2, portalescastillo2022pthfgf23klotho pages 3-5, agoro2023regulationoffgf23 pages 3-4) |
| Protein family and biochemical role | FGF23 is an endocrine member of the FGF/heparin-binding growth-factor family, but it is a signaling ligand rather than an enzyme or transporter; therefore, it has no catalytic substrate. Its principal physiological role is to function as a phosphaturic hormone coordinating phosphate and active-vitamin-D homeostasis. Its relatively weak heparan-sulfate affinity facilitates release from bone and endocrine circulation. | (agoro2023regulationoffgf23 pages 3-4, edmonston2024fgf23andklotho pages 2-4, agoro2023regulationoffgf23 pages 1-2) |
| Canonical receptor complex | Physiological signaling is mediated chiefly by an FGFR1c–α-Klotho complex. Structural studies also support α-Klotho-dependent complexes with FGFR3c and FGFR4. FGF23’s N-terminal region engages FGFR, whereas its C-terminal tail engages α-Klotho; α-Klotho stabilizes the primary ligand–receptor complex rather than acting as the catalytic receptor. | (edmonston2024fgf23andklotho pages 2-4, chen2023structuralbasisfor pages 2-3, chen2023structuralbasisfor pages 1-2) |
| Receptor activation mechanism | Cryo-EM structures reveal an asymmetric 1:2:1:1 FGF23–FGFR–α-Klotho–heparan-sulfate complex. Heparan sulfate enables the primary 1:1:1 complex to recruit a second FGFR, causing the receptor dimerization required for tyrosine-kinase activation; α-Klotho does not directly recruit the secondary receptor. | (chen2023structuralbasisfor pages 2-3, chen2023structuralbasisfor pages 1-2, chen2023structuralbasisfor pages 6-7) |
| Primary tissue source and localization | FGF23 is synthesized and secreted primarily by osteocytes and osteoblast-lineage cells in bone and enters the extracellular fluid and circulation. Bone-marrow stromal and erythroid cells can contribute under conditions such as anaemia or elevated erythropoietin. | (agoro2023regulationoffgf23 pages 1-2, agoro2023regulationoffgf23 pages 3-4, agoro2023regulationoffgf23 pages 2-3) |
| Principal target tissue | The kidney is the dominant endocrine target. In renal proximal tubules, FGF23 controls phosphate transport and vitamin-D metabolism; in distal tubules, it can enhance calcium and sodium reabsorption through TRPV5 and NCC, respectively. | (latic2022interactionofvitamin pages 5-7, agoro2023regulationoffgf23 pages 3-4, latic2022interactionofvitamin pages 7-8) |
| Additional target tissues | FGF23 can suppress PTH transcription and secretion in the parathyroid gland. Proposed or pathological targets include cardiomyocytes and cardiac fibroblasts; bone may also experience local auto/paracrine effects, although several non-renal effects remain context-dependent or incompletely resolved. | (dastghaib2023newconceptsin pages 1-2, martinezheredia2024nonclassicaleffectsof pages 2-4, martinezheredia2024nonclassicaleffectsof pages 4-5) |
| Canonical intracellular signaling | FGFR–α-Klotho engagement activates FRS2α and RAS–MAPK signaling, including ERK1/2. In proximal tubules, MAPK-linked EGR1 and ERK1/2–SGK1 contribute to transporter regulation and phosphaturia, although downstream control of vitamin-D-metabolizing genes is not fully mapped. | (edmonston2024fgf23andklotho pages 2-4, agoro2023regulationoffgf23 pages 3-4, agoro2023regulationoffgf23 pages 2-3, latic2022interactionofvitamin pages 14-15) |
| Phosphate metabolism | In the proximal-tubule apical membrane, FGF23 promotes internalization and degradation or downregulation of NPT2a/NaPi-IIa (SLC34A1) and NPT2c/NaPi-IIc (SLC34A3). This decreases filtered-phosphate reabsorption and increases urinary phosphate excretion. | (portalescastillo2022pthfgf23klotho pages 3-5, agoro2023regulationoffgf23 pages 3-4, agoro2023regulationoffgf23 pages 2-3) |
| Vitamin-D metabolism | FGF23 suppresses renal CYP27B1/1α-hydroxylase, reducing conversion of 25-hydroxyvitamin D to active 1,25-dihydroxyvitamin D (calcitriol), while inducing CYP24A1/24-hydroxylase and increasing vitamin-D catabolism. Lower calcitriol also reduces intestinal phosphate absorption. Calcitriol reciprocally stimulates bone FGF23 expression, forming a negative-feedback loop. | (agoro2023regulationoffgf23 pages 3-4, latic2022interactionofvitamin pages 7-8, latic2022interactionofvitamin pages 5-7) |
| Parathyroid-hormone axis | Under physiological conditions, FGF23 suppresses PTH through α-Klotho/ERK1/2-dependent and proposed calcineurin-dependent mechanisms. In advanced CKD, reduced parathyroid α-Klotho and FGFR1c expression can produce FGF23 resistance, while low calcitriol and calcium favor secondary hyperparathyroidism. | (martinezheredia2024nonclassicaleffectsof pages 2-4) |
| Mineral and endocrine regulation | Phosphate, calcium and calcium–phosphate calciprotein particles stimulate FGF23 production or increase intact-hormone stability. Calcitriol strongly induces transcription, and PTH generally increases FGF23 during sustained exposure, although acute effects can differ because PTH also changes phosphate balance and FGF23 cleavage. | (vervloet2022sheddinglighton pages 4-6, vervloet2022sheddinglighton pages 2-4, agoro2023regulationoffgf23 pages 2-3) |
| Local and kidney-derived regulation | PHEX and DMP1 normally restrain osteocytic FGF23; loss of either causes FGF23 excess and renal phosphate wasting. Erythropoietin, kidney-derived lipocalin-2, and the glycerol-3-phosphate–lysophosphatidic-acid pathway can stimulate production, particularly during anaemia, CKD or acute kidney injury. | (agoro2023regulationoffgf23 pages 1-2, vervloet2022sheddinglighton pages 4-6, agoro2023regulationoffgf23 pages 4-5, agoro2023regulationoffgf23 pages 3-4) |
| CKD and CKD–mineral and bone disorder | FGF23 rises early and progressively as kidney function declines, often before overt hyperphosphataemia or increased PTH. Initially it is adaptive, increasing fractional phosphate excretion and lowering calcitriol; in advanced disease, nephron loss and Klotho deficiency overwhelm this compensation, producing very high FGF23, phosphate retention, low calcitriol and secondary hyperparathyroidism. | (ponsbelda2023mineralmetabolismin pages 10-12, edmonston2024fgf23andklotho pages 4-5, vervloet2022sheddinglighton pages 4-6) |
| Pathological cardiovascular signaling | At markedly elevated concentrations, especially with CKD-associated Klotho deficiency, FGF23 can activate cardiomyocyte FGFR4 independently of α-Klotho. The FGFR4–PLCγ–calcineurin–NFAT pathway has been linked experimentally to left-ventricular hypertrophy, while WNT/β-catenin and TGF-β pathways may contribute to fibrosis. Causality in humans remains debated. | (martinezheredia2024nonclassicaleffectsof pages 4-5, edmonston2024fgf23andklotho pages 5-6, nakano2023directandindirect pages 2-3) |
| Clinical significance and applications | FGF23 excess causes renal phosphate wasting, hypophosphataemic rickets/osteomalacia and tumor-induced osteomalacia; deficient signaling or excessive cleavage produces hyperphosphataemia and ectopic calcification. FGF23 immunoassays are clinically established for diagnosing hereditary hypophosphataemic disorders and diagnosing or monitoring tumor-induced osteomalacia, but assays are not standardized and routine CKD risk-guided use remains unproven. | (portalescastillo2022pthfgf23klotho pages 3-5, latic2022interactionofvitamin pages 7-8, martinezheredia2024nonclassicaleffectsof pages 4-5) |
Table: This table integrates FGF23 structure, processing, receptor biology, tissue localization, signaling, mineral-metabolism functions, regulation, and clinical significance. It distinguishes the canonical bone–kidney endocrine pathway from less-certain pathological signaling in non-renal tissues.
FGF23 plays a central but ultimately maladaptive role in CKD-mineral and bone disorder (CKD-MBD) (ponsbelda2023mineralmetabolismin pages 10-12, edmonston2024fgf23andklotho pages 4-5, vervloet2022sheddinglighton pages 4-6). As kidney function declines, circulating FGF23 rises early and progressively, often before the development of overt hyperphosphatemia or increased PTH (ponsbelda2023mineralmetabolismin pages 10-12, edmonston2024fgf23andklotho pages 4-5). Initially, elevated FGF23 represents an adaptive response that increases fractional phosphate excretion by remaining nephrons and suppresses calcitriol to limit intestinal phosphate absorption (edmonston2024fgf23andklotho pages 4-5, vervloet2022sheddinglighton pages 4-6).
However, in advanced CKD, nephron loss and declining kidney α-Klotho expression overwhelm this compensatory mechanism (diazhaaz2025effectsoffibroblast pages 2-4, edmonston2024fgf23andklotho pages 4-5). The result is markedly elevated FGF23 (often 100- to 1000-fold above normal), phosphate retention, profoundly suppressed calcitriol, hypocalcemia, and severe secondary hyperparathyroidism (edmonston2024fgf23andklotho pages 4-5, latic2022interactionofvitamin pages 7-8). FGF23 may also contribute to CKD-associated bone disease by impairing bone mineralization and is associated with increased fracture risk (martinezheredia2024nonclassicaleffectsof pages 2-4, martinezheredia2024nonclassicaleffectsof pages 4-5).
Elevated FGF23 is strongly associated with adverse cardiovascular outcomes, particularly in CKD populations but also in the general population (diazhaaz2025effectsoffibroblast pages 4-5, martinezheredia2024nonclassicaleffectsof pages 4-5, nakano2023directandindirect pages 1-2). Epidemiological studies link higher FGF23 levels with left ventricular hypertrophy (LVH), heart failure, atrial fibrillation, and increased cardiovascular and all-cause mortality (diazhaaz2025effectsoffibroblast pages 4-5, martinezheredia2024nonclassicaleffectsof pages 4-5, nakano2023directandindirect pages 2-3).
Mechanistically, when FGF23 levels are extremely elevated and cardiac α-Klotho is deficient—as occurs in CKD—FGF23 can activate cardiomyocyte FGFR4 independently of α-Klotho (diazhaaz2025effectsoffibroblast pages 4-5, edmonston2024fgf23andklotho pages 5-6, nakano2023directandindirect pages 2-3). This activates the PLCγ–calcineurin–NFAT signaling pathway, promoting pathological cardiac hypertrophy, contractile dysfunction, and arrhythmias (diazhaaz2025effectsoffibroblast pages 4-5, edmonston2024fgf23andklotho pages 5-6, nakano2023directandindirect pages 7-7). FGF23 may also promote cardiac fibrosis through WNT/β-catenin and TGF-β pathways in cardiac fibroblasts (martinezheredia2024nonclassicaleffectsof pages 4-5, edmonston2024fgf23andklotho pages 5-6, nakano2023directandindirect pages 3-5).
Indirect cardiovascular effects occur through FGF23's suppression of renal active vitamin D synthesis. Reduced vitamin D activity stimulates the renin-angiotensin-aldosterone system (RAAS), which contributes to hypertension, cardiac hypertrophy, and fibrosis (nakano2023directandindirect pages 1-2, nakano2023directandindirect pages 3-5, diazhaaz2025effectsoffibroblast pages 1-2). FGF23 is also associated with endothelial dysfunction, reduced nitric oxide availability, and increased vascular oxidative stress, particularly when α-Klotho is deficient (diazhaaz2025effectsoffibroblast pages 4-5, martinezheredia2024nonclassicaleffectsof pages 4-5).
FGF23 excess causes a spectrum of hypophosphatemic disorders characterized by renal phosphate wasting, hypophosphatemia, and rickets or osteomalacia. X-linked hypophosphatemia results from loss-of-function mutations in PHEX, leading to increased FGF23 production (vervloet2022sheddinglighton pages 10-11, vervloet2022sheddinglighton pages 4-6). Autosomal-dominant hypophosphatemic rickets is caused by mutations at the FGF23 cleavage site (typically R176 or R179) that prevent proteolytic inactivation, resulting in excessive intact bioactive hormone (agoro2023regulationoffgf23 pages 1-2, portalescastillo2022pthfgf23klotho pages 3-5).
Tumor-induced osteomalacia occurs when mesenchymal tumors produce excessive FGF23, often driven by hypoxia-inducible factor pathways (vervloet2022sheddinglighton pages 10-11). Autosomal recessive hypophosphatemic rickets results from loss-of-function mutations in DMP1, derepressing FGF23 production (vervloet2022sheddinglighton pages 10-11, vervloet2022sheddinglighton pages 4-6).
FGF23 immunoassays are clinically established for diagnosing hereditary hypophosphatemic disorders and for diagnosing and monitoring tumor-induced osteomalacia (portalescastillo2022pthfgf23klotho pages 3-5). The monoclonal antibody burosumab, which neutralizes FGF23, has been approved for treating X-linked hypophosphatemia and tumor-induced osteomalacia, representing a milestone in targeting FGF23-mediated diseases (martinezheredia2024nonclassicaleffectsof pages 1-2). However, FGF23 assays are not standardized across platforms, requiring assay-specific reference ranges (portalescastillo2022pthfgf23klotho pages 3-5). While FGF23 predicts adverse outcomes in CKD, its routine use for risk stratification or as a therapeutic target in CKD remains unproven and requires dedicated prospective trials (portalescastillo2022pthfgf23klotho pages 3-5, edmonston2024fgf23andklotho pages 4-5).
FGF23 is a bone-derived endocrine hormone that serves as the principal phosphaturic regulator coordinating phosphate and vitamin D homeostasis. Produced primarily by osteocytes in response to elevated phosphate, calcium, vitamin D, and PTH, FGF23 acts through FGFR–α-Klotho complexes—predominantly FGFR1c, FGFR3c, and FGFR4—to activate MAPK/ERK signaling pathways. In the kidney, FGF23 downregulates sodium-phosphate cotransporters NPT2a and NPT2c to promote phosphaturia, while suppressing CYP27B1 and inducing CYP24A1 to reduce active vitamin D synthesis. FGF23 production is tightly regulated through transcriptional control, post-translational glycosylation by GALNT3 (which stabilizes intact hormone), and phosphorylation by FAM20C (which promotes cleavage). In CKD, progressively elevated FGF23 initially compensates for reduced phosphate excretion but ultimately becomes maladaptive, contributing to CKD-MBD and potentially to cardiovascular disease through klotho-independent FGFR4 signaling. FGF23 excess causes hypophosphatemic disorders, while FGF23-neutralizing antibodies represent an established therapeutic approach for these conditions.
References
(agoro2023regulationoffgf23 pages 3-4): Rafiou Agoro and Kenneth E. White. Regulation of fgf23 production and phosphate metabolism by bone–kidney interactions. Nature Reviews Nephrology, 19:185-193, Jan 2023. URL: https://doi.org/10.1038/s41581-022-00665-x, doi:10.1038/s41581-022-00665-x. This article has 119 citations and is from a domain leading peer-reviewed journal.
(edmonston2024fgf23andklotho pages 2-4): Daniel Edmonston, Alexander Grabner, and Myles Wolf. Fgf23 and klotho at the intersection of kidney and cardiovascular disease. Nature Reviews Cardiology, 21:11-24, Jul 2024. URL: https://doi.org/10.1038/s41569-023-00903-0, doi:10.1038/s41569-023-00903-0. This article has 170 citations and is from a domain leading peer-reviewed journal.
(agoro2023regulationoffgf23 pages 1-2): Rafiou Agoro and Kenneth E. White. Regulation of fgf23 production and phosphate metabolism by bone–kidney interactions. Nature Reviews Nephrology, 19:185-193, Jan 2023. URL: https://doi.org/10.1038/s41581-022-00665-x, doi:10.1038/s41581-022-00665-x. This article has 119 citations and is from a domain leading peer-reviewed journal.
(dastghaib2023newconceptsin pages 2-4): Sanaz Dastghaib, Farhad Koohpeyma, Mesbah Shams, Forough Saki, and Aliakbar Alizadeh. New concepts in regulation and function of the fgf23. Clinical and Experimental Medicine, 23:1055-1066, Jun 2023. URL: https://doi.org/10.1007/s10238-022-00844-x, doi:10.1007/s10238-022-00844-x. This article has 27 citations and is from a peer-reviewed journal.
(portalescastillo2022pthfgf23klotho pages 3-5): Ignacio A. Portales-Castillo and Petra Simic. Pth, fgf-23, klotho and vitamin d as regulators of calcium and phosphorus: genetics, epigenetics and beyond. Frontiers in Endocrinology, Sep 2022. URL: https://doi.org/10.3389/fendo.2022.992666, doi:10.3389/fendo.2022.992666. This article has 116 citations.
(dastghaib2023newconceptsin pages 1-2): Sanaz Dastghaib, Farhad Koohpeyma, Mesbah Shams, Forough Saki, and Aliakbar Alizadeh. New concepts in regulation and function of the fgf23. Clinical and Experimental Medicine, 23:1055-1066, Jun 2023. URL: https://doi.org/10.1007/s10238-022-00844-x, doi:10.1007/s10238-022-00844-x. This article has 27 citations and is from a peer-reviewed journal.
(agoro2023regulationoffgf23 pages 2-3): Rafiou Agoro and Kenneth E. White. Regulation of fgf23 production and phosphate metabolism by bone–kidney interactions. Nature Reviews Nephrology, 19:185-193, Jan 2023. URL: https://doi.org/10.1038/s41581-022-00665-x, doi:10.1038/s41581-022-00665-x. This article has 119 citations and is from a domain leading peer-reviewed journal.
(latic2022interactionofvitamin pages 5-7): Nejla Latic and Reinhold G. Erben. Interaction of vitamin d with peptide hormones with emphasis on parathyroid hormone, fgf23, and the renin-angiotensin-aldosterone system. Nutrients, 14:5186, Dec 2022. URL: https://doi.org/10.3390/nu14235186, doi:10.3390/nu14235186. This article has 82 citations.
(latic2022interactionofvitamin pages 7-8): Nejla Latic and Reinhold G. Erben. Interaction of vitamin d with peptide hormones with emphasis on parathyroid hormone, fgf23, and the renin-angiotensin-aldosterone system. Nutrients, 14:5186, Dec 2022. URL: https://doi.org/10.3390/nu14235186, doi:10.3390/nu14235186. This article has 82 citations.
(martinezheredia2024nonclassicaleffectsof pages 2-4): Luis Martínez-Heredia, Juan Manuel Canelo-Moreno, Beatriz García-Fontana, and Manuel Muñoz-Torres. Non-classical effects of fgf23: molecular and clinical features. International Journal of Molecular Sciences, 25:4875, Apr 2024. URL: https://doi.org/10.3390/ijms25094875, doi:10.3390/ijms25094875. This article has 39 citations.
(martinezheredia2024nonclassicaleffectsof pages 4-5): Luis Martínez-Heredia, Juan Manuel Canelo-Moreno, Beatriz García-Fontana, and Manuel Muñoz-Torres. Non-classical effects of fgf23: molecular and clinical features. International Journal of Molecular Sciences, 25:4875, Apr 2024. URL: https://doi.org/10.3390/ijms25094875, doi:10.3390/ijms25094875. This article has 39 citations.
(diazhaaz2025effectsoffibroblast pages 4-5): Diego Ivan Diaz-Haaz, Eleasib Alejandro Espinoza-Pérez, Jesús Armando Aguilar-Alonso, Mauricio Megchún-Hernández, Fernando Gonzalez-Diaz, and Néstor Rodolfo García-Chong. Effects of fibroblast growth factor 23 (fgf23) on the cardiovascular system: a review of literature. Cureus, Nov 2025. URL: https://doi.org/10.7759/cureus.97147, doi:10.7759/cureus.97147. This article has 6 citations.
(edmonston2024fgf23andklotho pages 5-6): Daniel Edmonston, Alexander Grabner, and Myles Wolf. Fgf23 and klotho at the intersection of kidney and cardiovascular disease. Nature Reviews Cardiology, 21:11-24, Jul 2024. URL: https://doi.org/10.1038/s41569-023-00903-0, doi:10.1038/s41569-023-00903-0. This article has 170 citations and is from a domain leading peer-reviewed journal.
(chen2023structuralbasisfor pages 1-2): Lingfeng Chen, Li-li Fu, Jingchuan Sun, Zhiqiang Huang, Mingzhen Fang, Allen P. Zinkle, Xin Liu, Junliang Lu, Zixiang Pan, Yang Wang, Guang Liang, Xiaokun Li, Gaozhi Chen, and M. Mohammadi. Structural basis for fgf hormone signalling. Nature, 618:862-870, Jun 2023. URL: https://doi.org/10.1038/s41586-023-06155-9, doi:10.1038/s41586-023-06155-9. This article has 166 citations and is from a highest quality peer-reviewed journal.
(chen2023structuralbasisfor pages 2-3): Lingfeng Chen, Li-li Fu, Jingchuan Sun, Zhiqiang Huang, Mingzhen Fang, Allen P. Zinkle, Xin Liu, Junliang Lu, Zixiang Pan, Yang Wang, Guang Liang, Xiaokun Li, Gaozhi Chen, and M. Mohammadi. Structural basis for fgf hormone signalling. Nature, 618:862-870, Jun 2023. URL: https://doi.org/10.1038/s41586-023-06155-9, doi:10.1038/s41586-023-06155-9. This article has 166 citations and is from a highest quality peer-reviewed journal.
(chen2023structuralbasisfor pages 6-7): Lingfeng Chen, Li-li Fu, Jingchuan Sun, Zhiqiang Huang, Mingzhen Fang, Allen P. Zinkle, Xin Liu, Junliang Lu, Zixiang Pan, Yang Wang, Guang Liang, Xiaokun Li, Gaozhi Chen, and M. Mohammadi. Structural basis for fgf hormone signalling. Nature, 618:862-870, Jun 2023. URL: https://doi.org/10.1038/s41586-023-06155-9, doi:10.1038/s41586-023-06155-9. This article has 166 citations and is from a highest quality peer-reviewed journal.
(latic2022interactionofvitamin pages 14-15): Nejla Latic and Reinhold G. Erben. Interaction of vitamin d with peptide hormones with emphasis on parathyroid hormone, fgf23, and the renin-angiotensin-aldosterone system. Nutrients, 14:5186, Dec 2022. URL: https://doi.org/10.3390/nu14235186, doi:10.3390/nu14235186. This article has 82 citations.
(prudhomme2024antiinflammatoryroleof pages 3-5): Gérald J. Prud'homme and Qinghua Wang. Anti-inflammatory role of the klotho protein and relevance to aging. Unknown journal, Aug 2024. URL: https://doi.org/10.20944/preprints202408.0213.v2, doi:10.20944/preprints202408.0213.v2.
(nakano2023directandindirect pages 2-3): Toshiaki Nakano, Hiroshi Kishimoto, and Masanori Tokumoto. Direct and indirect effects of fibroblast growth factor 23 on the heart. Frontiers in Endocrinology, Feb 2023. URL: https://doi.org/10.3389/fendo.2023.1059179, doi:10.3389/fendo.2023.1059179. This article has 46 citations.
(agoro2023regulationoffgf23 pages 7-8): Rafiou Agoro and Kenneth E. White. Regulation of fgf23 production and phosphate metabolism by bone–kidney interactions. Nature Reviews Nephrology, 19:185-193, Jan 2023. URL: https://doi.org/10.1038/s41581-022-00665-x, doi:10.1038/s41581-022-00665-x. This article has 119 citations and is from a domain leading peer-reviewed journal.
(latic2022interactionofvitamin pages 2-4): Nejla Latic and Reinhold G. Erben. Interaction of vitamin d with peptide hormones with emphasis on parathyroid hormone, fgf23, and the renin-angiotensin-aldosterone system. Nutrients, 14:5186, Dec 2022. URL: https://doi.org/10.3390/nu14235186, doi:10.3390/nu14235186. This article has 82 citations.
(martinezheredia2024nonclassicaleffectsof pages 1-2): Luis Martínez-Heredia, Juan Manuel Canelo-Moreno, Beatriz García-Fontana, and Manuel Muñoz-Torres. Non-classical effects of fgf23: molecular and clinical features. International Journal of Molecular Sciences, 25:4875, Apr 2024. URL: https://doi.org/10.3390/ijms25094875, doi:10.3390/ijms25094875. This article has 39 citations.
(portalescastillo2022pthfgf23klotho pages 5-7): Ignacio A. Portales-Castillo and Petra Simic. Pth, fgf-23, klotho and vitamin d as regulators of calcium and phosphorus: genetics, epigenetics and beyond. Frontiers in Endocrinology, Sep 2022. URL: https://doi.org/10.3389/fendo.2022.992666, doi:10.3389/fendo.2022.992666. This article has 116 citations.
(edmonston2024fgf23andklotho pages 4-5): Daniel Edmonston, Alexander Grabner, and Myles Wolf. Fgf23 and klotho at the intersection of kidney and cardiovascular disease. Nature Reviews Cardiology, 21:11-24, Jul 2024. URL: https://doi.org/10.1038/s41569-023-00903-0, doi:10.1038/s41569-023-00903-0. This article has 170 citations and is from a domain leading peer-reviewed journal.
(vervloet2022sheddinglighton pages 10-11): Marc G. Vervloet. Shedding light on the complex regulation of fgf23. Metabolites, 12:401, Apr 2022. URL: https://doi.org/10.3390/metabo12050401, doi:10.3390/metabo12050401. This article has 22 citations.
(vervloet2022sheddinglighton pages 2-4): Marc G. Vervloet. Shedding light on the complex regulation of fgf23. Metabolites, 12:401, Apr 2022. URL: https://doi.org/10.3390/metabo12050401, doi:10.3390/metabo12050401. This article has 22 citations.
(vervloet2022sheddinglighton pages 1-2): Marc G. Vervloet. Shedding light on the complex regulation of fgf23. Metabolites, 12:401, Apr 2022. URL: https://doi.org/10.3390/metabo12050401, doi:10.3390/metabo12050401. This article has 22 citations.
(vervloet2022sheddinglighton pages 4-6): Marc G. Vervloet. Shedding light on the complex regulation of fgf23. Metabolites, 12:401, Apr 2022. URL: https://doi.org/10.3390/metabo12050401, doi:10.3390/metabo12050401. This article has 22 citations.
(agoro2023regulationoffgf23 pages 4-5): Rafiou Agoro and Kenneth E. White. Regulation of fgf23 production and phosphate metabolism by bone–kidney interactions. Nature Reviews Nephrology, 19:185-193, Jan 2023. URL: https://doi.org/10.1038/s41581-022-00665-x, doi:10.1038/s41581-022-00665-x. This article has 119 citations and is from a domain leading peer-reviewed journal.
(ponsbelda2023mineralmetabolismin pages 10-12): Oscar D. Pons-Belda, Mª Agustina Alonso-Álvarez, Juan David González-Rodríguez, Laura Mantecón-Fernández, and Fernando Santos-Rodríguez. Mineral metabolism in children: interrelation between vitamin d and fgf23. International Journal of Molecular Sciences, 24:6661, Apr 2023. URL: https://doi.org/10.3390/ijms24076661, doi:10.3390/ijms24076661. This article has 25 citations.
(diazhaaz2025effectsoffibroblast pages 2-4): Diego Ivan Diaz-Haaz, Eleasib Alejandro Espinoza-Pérez, Jesús Armando Aguilar-Alonso, Mauricio Megchún-Hernández, Fernando Gonzalez-Diaz, and Néstor Rodolfo García-Chong. Effects of fibroblast growth factor 23 (fgf23) on the cardiovascular system: a review of literature. Cureus, Nov 2025. URL: https://doi.org/10.7759/cureus.97147, doi:10.7759/cureus.97147. This article has 6 citations.
(nakano2023directandindirect pages 1-2): Toshiaki Nakano, Hiroshi Kishimoto, and Masanori Tokumoto. Direct and indirect effects of fibroblast growth factor 23 on the heart. Frontiers in Endocrinology, Feb 2023. URL: https://doi.org/10.3389/fendo.2023.1059179, doi:10.3389/fendo.2023.1059179. This article has 46 citations.
(nakano2023directandindirect pages 7-7): Toshiaki Nakano, Hiroshi Kishimoto, and Masanori Tokumoto. Direct and indirect effects of fibroblast growth factor 23 on the heart. Frontiers in Endocrinology, Feb 2023. URL: https://doi.org/10.3389/fendo.2023.1059179, doi:10.3389/fendo.2023.1059179. This article has 46 citations.
(nakano2023directandindirect pages 3-5): Toshiaki Nakano, Hiroshi Kishimoto, and Masanori Tokumoto. Direct and indirect effects of fibroblast growth factor 23 on the heart. Frontiers in Endocrinology, Feb 2023. URL: https://doi.org/10.3389/fendo.2023.1059179, doi:10.3389/fendo.2023.1059179. This article has 46 citations.
(diazhaaz2025effectsoffibroblast pages 1-2): Diego Ivan Diaz-Haaz, Eleasib Alejandro Espinoza-Pérez, Jesús Armando Aguilar-Alonso, Mauricio Megchún-Hernández, Fernando Gonzalez-Diaz, and Néstor Rodolfo García-Chong. Effects of fibroblast growth factor 23 (fgf23) on the cardiovascular system: a review of literature. Cureus, Nov 2025. URL: https://doi.org/10.7759/cureus.97147, doi:10.7759/cureus.97147. This article has 6 citations.