The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
The supplied identity is internally consistent and is supported by the literature: Mus musculus Alpl, historically Akp2, encodes tissue-nonspecific alkaline phosphatase (TNAP/TNSALP), the liver–bone–kidney alkaline-phosphatase isozyme. It is distinct from the other mouse alkaline-phosphatase genes Akp3, Akp5 and Akp6. Its conserved alkaline-phosphatase fold, catalytic metal sites and GPI-anchor topology agree with the supplied InterPro/Pfam annotations; no conflicting same-symbol protein was encountered. The literature does not routinely cite accession P09242, so accession-to-sequence mapping rests on the supplied UniProt record, whereas gene/protein identity is independently verified by mouse literature. (liedtke2020tissuenonspecificalkalinephosphatase—a pages 1-3, buchet2013multisystemicfunctionsof pages 1-3, buchet2013multisystemicfunctionsof pages 4-6)
The best-supported primary function is local control of phosphate compounds at biological membranes. In mineralizing tissues, TNAP hydrolyzes extracellular inorganic pyrophosphate (PPi), simultaneously removing a potent hydroxyapatite-growth inhibitor and generating inorganic phosphate (Pi). In other contexts it dephosphorylates pyridoxal-5′-phosphate (PLP), extracellular nucleotides, and—in thermogenic brown/beige adipocytes—mitochondrial phosphocreatine. Thus, “tissue-nonspecific” does not mean functionally indiscriminate in vivo: substrate use is determined by localization, substrate availability and tissue state. (buchet2013multisystemicfunctionsof pages 6-9, orimo2010themechanismof pages 3-4, sun2021mitochondrialtnapcontrols pages 2-4, imam2024structuralandfunctional pages 15-17)
| Biochemical reaction / substrate | Principal cellular location | Biological consequence / pathway | Evidence type and confidence | Key quantitative result |
|---|---|---|---|---|
| Inorganic pyrophosphate: PPi + H₂O → 2 Pi | Extracellular face of osteoblast and hypertrophic-chondrocyte membranes; osteoblast/chondrocyte matrix vesicles | Removes PPi-mediated inhibition of hydroxyapatite growth and increases local Pi, enabling propagation of skeletal and dental mineral beyond matrix vesicles | Direct mouse knockout, localization, metabolite-accumulation and rescue evidence; very high confidence (buchet2013multisystemicfunctionsof pages 6-9, orimo2010themechanismof pages 3-4, sato2021tissuenonspecificalkalinephosphatase pages 6-8) | Skeletal defects emerge around postnatal day 10 in Alpl-null mice; heterozygotes retain about 50% of wild-type plasma ALP activity (sato2021tissuenonspecificalkalinephosphatase pages 6-8) |
| Pyridoxal-5′-phosphate: PLP + H₂O → pyridoxal + Pi | Extracellular cell surface, including neural and vascular compartments | Produces membrane-transportable pyridoxal for intracellular vitamin-B6 salvage and regeneration of PLP; supports PLP-dependent neurotransmitter metabolism and limits vitamin-B6-responsive seizures | Direct mouse substrate accumulation, knockout phenotype and pyridoxal rescue; very high confidence (orimo2010themechanismof pages 3-4, sato2021tissuenonspecificalkalinephosphatase pages 6-8) | Alpl-null mice have elevated plasma PLP and fatal CNS seizures; pyridoxal plus semisolid diet rescues seizures, although dental disease subsequently develops (sato2021tissuenonspecificalkalinephosphatase pages 6-8) |
| ATP → ADP → AMP → adenosine/Pi-associated products | Extracellular-facing GPI-anchored TNAP on plasma membranes; reported in neural, endothelial and mesenchymal-cell environments | Regulates extracellular nucleotide availability, purinergic-receptor signaling and ATP-dependent mesenchymal-stem-cell physiology | Broad biochemical specificity plus mouse genetic/pharmacological evidence; moderate-to-high confidence, with physiological importance dependent on cell context (buchet2013multisystemicfunctionsof pages 6-9, liedtke2020tissuenonspecificalkalinephosphatase—a pages 1-3, sebastianserrano2016neurodevelopmentalalterationsand pages 1-2) | P2X7-receptor blockade prevented convulsions and prolonged survival in TNAP-null mice; exogenous ATP or TNAP antagonists induced P2X7-dependent seizures in adult wild-type mice (sebastianserrano2016neurodevelopmentalalterationsand pages 1-2) |
| Phosphocreatine: PCr + H₂O → creatine + Pi | GPI-linked TNAP at the mitochondrial inner membrane/intermembrane-space region of mouse brown and beige thermogenic adipocytes | Drives the futile creatine cycle, coupling repeated PCr hydrolysis and rephosphorylation to adaptive heat production | Direct mouse biochemical purification, imaging, selective inhibition and adipocyte-specific deletion; high confidence in thermogenic adipocytes, not established as a universal TNAP location (sun2021mitochondrialtnapcontrols pages 2-4, sun2021mitochondrialtnapcontrols pages 4-6, sun2021mitochondrialtnapcontrols pages 34-36) | Cold increased Alpl expression 31.4-fold in brown fat and 18.8-fold in beige fat; inhibition raised mitochondrial PCr by 65% and reduced β3-adrenergic-stimulated energy expenditure by 30% (sun2021mitochondrialtnapcontrols pages 2-4, sun2021mitochondrialtnapcontrols pages 4-6) |
| Broad phosphate-monoester hydrolysis; physiological matrix-vesicle activity is dominated by local PPi control | TNAP is enriched on matrix vesicles released by osteoblasts and growth-plate chondrocytes | Supports extravesicular crystal growth and collagen-matrix mineral propagation rather than being solely responsible for initial intravesicular crystal nucleation | Direct mouse expression/localization and Alpl-null mineralization pathology; high confidence (buchet2013multisystemicfunctionsof pages 6-9, buchet2013multisystemicfunctionsof pages 4-6) | Crystals can initiate within Alpl-null matrix vesicles but fail to grow normally after vesicle rupture, separating TNAP-dependent propagation from initial nucleation (buchet2013multisystemicfunctionsof pages 6-9) |
| Conserved alkaline-phosphatase catalytic mechanism with broad phosphate-substrate recognition | Usually an extracellular-facing, GPI-anchored glycoprotein dimer; human TNAP can assemble into octamers | Two catalytic Zn²⁺ ions and one Mg²⁺ support catalysis; a further Ca²⁺ site is described; crown and substrate-access regions contribute to isozyme behavior and broad specificity | Mammalian comparative biochemistry plus human ortholog structural evidence, not a direct mouse structure; high confidence for conserved architecture (liedtke2020tissuenonspecificalkalinephosphatase—a pages 1-3, buchet2013multisystemicfunctionsof pages 4-6, yu2023thestructuralpathology pages 1-2) | Human TNAP structures were resolved at approximately 2.9 Å under acidic and 3.2 Å under basic conditions; dimer predominated in solution, with an unexpected dimer-derived octamer also observed (yu2023thestructuralpathology pages 1-2) |
Table: Compact evidence map linking mouse TNAP substrates and locations to mineralization, vitamin-B6 metabolism, purinergic signaling, and thermogenesis. Direct mouse findings are distinguished from conserved human structural evidence.
Mouse Alpl/Akp2 maps to the tissue-nonspecific branch of the mammalian alkaline-phosphatase multigene family. Expression is broad—including bone, cartilage, teeth, liver, kidney, endothelium and neural tissues—unlike more restricted intestinal or embryonic paralogs. This matches the designation “liver/bone/kidney isozyme” but does not imply uniform abundance or function in every tissue. (buchet2013multisystemicfunctionsof pages 1-3, buchet2013multisystemicfunctionsof pages 4-6)
TNAP is synthesized as a precursor glycoprotein, dimerizes during maturation, and is usually attached to the outer leaflet of the plasma membrane by a C-terminal glycosylphosphatidylinositol (GPI) anchor, leaving the catalytic face extracellular. It can also be enriched on osteoblast- and chondrocyte-derived matrix vesicles or released into circulation after anchor cleavage. Each conventional monomeric active site contains two Zn²⁺ ions and one Mg²⁺; a further Ca²⁺-binding site is described but is not considered part of the catalytic tri-metal center. The crown domain contributes extracellular-matrix interactions and isozyme-specific behavior. (liedtke2020tissuenonspecificalkalinephosphatase—a pages 1-3, buchet2013multisystemicfunctionsof pages 4-6)
The 2024 evolutionary analysis places TNAP in the alkaline-phosphatase superfamily, whose members share a central mixed β-sheet flanked by α-helices and conserved catalytic/metal-binding residues. Differences in charge, hydrophobicity and accessibility around substrate-recognition regions—not wholesale changes to the catalytic core—help explain divergent substrate preferences among family members. This architecture is concordant with the supplied Alkaline_phosphatase/PF00245 domains. (imam2024structuralandfunctional pages 1-2, imam2024structuralandfunctional pages 15-17)
A major 2023 structural advance came from human TNAP, not mouse TNAP. Crystal structures at approximately 2.9 Å under acidic and 3.2 Å under basic conditions showed that dimers predominate in solution but can form an unexpected octamer assembled from TNAP dimers. More than 400 reported pathogenic human alleles could thereby be interpreted in structural context. Because the catalytic core is strongly conserved, these structures are informative for mouse P09242, but oligomeric state and mutation effects should formally be treated as ortholog-based inference rather than direct mouse structural evidence. (yu2023thestructuralpathology pages 1-2)
As an alkaline phosphatase, TNAP catalyzes hydrolysis of phosphate monoesters:
R–O–PO₃²⁻ + H₂O → R–OH + Pi.
It also hydrolyzes PPi:
PPi + H₂O → 2 Pi.
Activity is favored at alkaline pH in vitro, approximately pH 8–10. TNAP displays broad activity against artificial and biological substrates—including ATP, ADP, AMP, glucose phosphates and β-glycerophosphate—but activity in an assay does not by itself establish physiological substrate status. PPi and PLP have the strongest classical in-vivo support; ATP-family nucleotides and phosphocreatine have compelling context-specific mouse evidence. Phosphoethanolamine accumulates in TNAP deficiency and is a clinical biomarker, but whether it is a direct physiological TNAP substrate remains less secure than PPi or PLP. (buchet2013multisystemicfunctionsof pages 6-9, orimo2010themechanismof pages 3-4)
At mineralizing surfaces, TNAP hydrolyzes extracellular PPi. Because PPi inhibits hydroxyapatite crystal growth, this reaction raises the local Pi/PPi ratio through two complementary effects: destruction of inhibitor and production of mineral precursor Pi. TNAP therefore permits calcium-phosphate crystals to expand into extracellular collagenous matrix. (buchet2013multisystemicfunctionsof pages 6-9, orimo2010themechanismof pages 3-4, imam2024structuralandfunctional pages 1-2)
The pathway is distributed across several proteins. ENPP1 generates extracellular PPi from nucleotides, ANKH regulates extracellular PPi availability, PHOSPHO1 helps produce Pi inside matrix vesicles, and TNAP removes PPi primarily at vesicle and cell surfaces. Crystals can begin inside matrix vesicles in Alpl-null material yet fail to grow normally after vesicle rupture. TNAP is therefore particularly important for crystal propagation, rather than being the sole initiator of intravesicular nucleation. (buchet2013multisystemicfunctionsof pages 6-9, orimo2010themechanismof pages 3-4)
Mouse genetic interaction supports this model: reducing or deleting PPi-generating Enpp1 alleviates aspects of TNAP-null skull and long-bone hypomineralization and reduces craniosynostosis incidence, although rescue is incomplete and tissue dependent. This is strong causal evidence that excess PPi—not merely loss of an osteoblast marker—is central to the Alpl-null skeletal phenotype. (nam2022deletionofthe pages 12-13)
Extracellular PLP cannot efficiently traverse membranes. TNAP dephosphorylates PLP to pyridoxal, which can enter cells and subsequently be rephosphorylated. Loss of Alpl therefore produces high extracellular/plasma PLP but inadequate intracellular availability of usable vitamin-B6 vitamer in critical neural settings, compromising PLP-dependent neurotransmitter metabolism. (orimo2010themechanismof pages 3-4, sato2021tissuenonspecificalkalinephosphatase pages 6-8)
Alpl-null mice develop fatal, vitamin-B6-responsive seizures; pyridoxal treatment can suppress seizures and prolong survival, exposing later skeletal and dental disease. This constitutes direct genetic and substrate-rescue evidence for PLP as a physiological TNAP substrate. (sato2021tissuenonspecificalkalinephosphatase pages 6-8)
TNAP can sequentially dephosphorylate ATP, ADP and AMP, thereby changing both ligand concentrations at P2 receptors and downstream adenosine/P1 signaling. Its quantitative importance varies by cell type because several ectonucleotidases share this chemistry. Consequently, TNAP should be annotated as a contributor to extracellular nucleotide homeostasis, not necessarily the universal dominant ATP ectophosphatase. (buchet2013multisystemicfunctionsof pages 6-9, liedtke2020tissuenonspecificalkalinephosphatase—a pages 1-3, imam2024structuralandfunctional pages 15-17)
In Alpl-null mice, increased neural-precursor proliferation, altered neuronal morphology and hyperactivity were associated with partial P2X7-receptor downregulation. P2X7 blockade prevented convulsions and extended survival, whereas ATP or TNAP antagonists induced P2X7-dependent seizures in adult wild-type mice. These findings connect TNAP activity to purinergic tone in vivo, while also showing that the seizure mechanism is broader than a simple PLP-deficiency model. (sebastianserrano2016neurodevelopmentalalterationsand pages 1-2)
A distinct mouse function was identified in 2021: in brown and beige adipocytes, TNAP hydrolyzes phosphocreatine (PCr → creatine + Pi) in mitochondria. Rephosphorylation of the released creatine consumes high-energy phosphate, producing a futile creatine cycle that supports heat generation. (sun2021mitochondrialtnapcontrols pages 2-4, sun2021mitochondrialtnapcontrols pages 1-2)
Biochemical purification found Alpl/TNAP sevenfold enriched in the active mitochondrial phosphocreatine-phosphatase fraction. Cold induced Alpl expression 31.4-fold in brown fat and 18.8-fold in beige fat. Selective TNAP inhibition increased mitochondrial PCr by 65%, abolished creatine-stimulated respiration under limiting ADP, and reduced β3-adrenergic-stimulated whole-body energy expenditure by 30% without changing basal respiration, movement or food intake. Adipocyte-specific Alpl knockout eliminated the inhibitor response and accelerated fat gain during high-fat feeding. (sun2021mitochondrialtnapcontrols pages 2-4, sun2021mitochondrialtnapcontrols pages 4-6)
This function involves an unusual localization: GPI-linked TNAP was visualized near cristae at the mitochondrial inner-membrane/intermembrane-space compartment in thermogenic adipocytes. PI-PLC release, protease protection, HSP60 colocalization and APEX2 electron microscopy support the assignment. It was not observed in examined hepatocytes and should not replace the canonical extracellular annotation; rather, it is a specialized, cell-state-dependent localization. (sun2021mitochondrialtnapcontrols pages 2-4, sun2021mitochondrialtnapcontrols pages 4-6, sun2021mitochondrialtnapcontrols pages 34-36)
The principal functional compartment is the extracellular face of the plasma membrane. In bone and growth plates, TNAP occurs on osteoblasts, hypertrophic chondrocytes and their matrix vesicles; in teeth it is associated with odontoblast/cementum-related mineralizing compartments. Its expression precedes mineral deposition, colocalizes with mineralization fronts and decreases as mineralization matures. (buchet2013multisystemicfunctionsof pages 6-9, orimo2010themechanismof pages 3-4)
Alpl is also expressed in renal tubules, biliary canaliculi, endothelium, neural tube and brain. In the nervous system and cerebral microvasculature, its surface orientation is compatible with PLP and nucleotide metabolism, although many proposed barrier, inflammatory and developmental functions remain less mechanistically settled than skeletal PPi hydrolysis. (buchet2013multisystemicfunctionsof pages 1-3, buchet2013multisystemicfunctionsof pages 4-6)
The mitochondrial localization in thermogenic adipocytes and reports of intracellular TNAP in bone/muscle progenitors indicate that annotation as exclusively extracellular is incomplete. Nevertheless, these intracellular pools are specialized and should not be generalized to all Alpl-expressing cells. (sun2021mitochondrialtnapcontrols pages 2-4, sun2021mitochondrialtnapcontrols pages 4-6)
Global Alpl/Akp2-null mice model severe infantile hypophosphatasia. They accumulate PPi and PLP, show impaired growth, vitamin-B6-dependent seizures, apnea and death before weaning. Skeletal abnormalities become evident around postnatal day 10 and progress to osteopenia and fractures; teeth and periodontal attachment are also affected. Heterozygotes retain about 50% of wild-type plasma ALP activity and are generally healthy and fertile, indicating substantial activity reserve under standard laboratory conditions. (sato2021tissuenonspecificalkalinephosphatase pages 6-8, buchet2013multisystemicfunctionsof pages 1-3)
Mineral-targeted recombinant TNAP rescues skeletal disease and epilepsy in knockout mice. The ability of circulating, mineral-targeted or soluble enzymes to rescue disease shows that native membrane attachment is not intrinsically required for catalysis; its physiological value is to concentrate TNAP near substrates and mineralization fronts. Daily soluble chimeric AP from postnatal day 1 prevented seizures and extended survival as far as the 53-day experimental period, with dose groups of 1, 8 and 16 mg/kg/day. (buchet2013multisystemicfunctionsof pages 6-9, gasque2015improvementofthe pages 3-4)
Gene therapy further supports enzyme causality. A single intramuscular dose of 3 × 10¹¹ vector genomes per mouse of AAV8-TNAP-D10 within five postnatal days was tested in 11 Alpl-null mice. It increased serum ALP, suppressed plasma PPi, prevented overt rickets and fractures, and produced broadly wild-type-like bone and dentoalveolar tissues over 70 days, with small residual cortical/trabecular and dental-density defects. No ectopic calcification was found in kidney, aorta, coronary arteries or brain during that observation window. (kinoshita2021genetherapyusing pages 1-2)
Structural pathology and agonist antibodies (July 2023). Near-atomic human TNAP structures defined pH-dependent structures and higher-order octamerization. The agonist antibody JTALP001 bound the octameric interface, enhanced osteoblast mineralization and augmented recombinant-TNAP rescue of TNAP-null osteoblasts. This introduces activation/stabilization of residual TNAP as a possible strategy, but the evidence remains preclinical and largely human-protein/cell based. DOI: 10.1038/s41467-023-39833-3. (yu2023thestructuralpathology pages 1-2)
Cell-autonomous cranial function (October 2023). Cranial-neural-crest-specific Alpl deletion caused skull-shape defects and deficient intersphenoid-synchondrosis growth, with altered chondrocyte proliferation, apoptosis, Sox9, PTHrP and IHH signaling. This refines the global-knockout interpretation by demonstrating a local requirement for TNAP in growth-plate maturation, likely mediated by Pi/PPi balance. DOI: 10.3390/ijms242015401.
Refined evolutionary/substrate framework (November 2024). Comparative analysis emphasized that conserved catalytic chemistry is combined with differences in substrate-pocket accessibility and electrostatics, and highlighted functional coupling between TNAP and ENPP enzymes in nucleotide, choline-lipid and mineralization pathways. DOI: 10.3390/metabo14120659. (imam2024structuralandfunctional pages 1-2, imam2024structuralandfunctional pages 15-17)
Current expert interpretation. Recent reviews increasingly frame TNAP as a compartment-specific metabolic enzyme rather than only an osteoblast differentiation marker. However, PPi hydrolysis in mineralization and PLP hydrolysis in vitamin-B6 salvage remain much more firmly established than proposed functions in lipid transport, inflammation or stem-cell maturation. The phosphocreatine function is strongly supported in mouse thermogenic adipocytes but is tissue restricted. (imam2024structuralandfunctional pages 1-2, sun2021mitochondrialtnapcontrols pages 2-4, sun2021mitochondrialtnapcontrols pages 4-6)
The direct human ortholog of mouse Alpl is ALPL, whose loss causes hypophosphatasia. Open Targets identifies strong ALPL associations with perinatal/infantile, childhood, adult and odonto-hypophosphatasia. These human associations corroborate the mouse model but should not be confused with an independent mouse disease annotation. (OpenTargets Search: -ALPL)
Asfotase alfa is a mineral-targeted recombinant TNAP enzyme that operationalizes the central mechanistic insight: restoring PPi hydrolysis near hydroxyapatite corrects mineralization while systemic enzyme activity also helps control other accumulated substrates. Mouse rescue studies were foundational to this approach. Current research explores soluble enzymes, longer-lived constructs, AAV-mediated TNAP delivery and TNAP-agonist antibodies. The AAV approach may reduce injection frequency, but persistent expression, immunogenicity, dose control and ectopic-calcification risk require longer follow-up than the 70-day mouse window. (buchet2013multisystemicfunctionsof pages 6-9, yu2023thestructuralpathology pages 1-2, kinoshita2021genetherapyusing pages 1-2, gasque2015improvementofthe pages 3-4)
TNAP is also used extensively as a histochemical marker of osteoblast differentiation, pluripotent cells and mineralizing cultures. This is an application of its high activity and expression pattern, not proof that every correlation with ALP staining reflects a causal Alpl pathway. Conversely, TNAP inhibition is being investigated for pathological vascular calcification and metabolic control, but systemic inhibition risks reproducing skeletal, dental, neural and thermogenic deficits demonstrated in mice. (sato2021tissuenonspecificalkalinephosphatase pages 23-24, liedtke2020tissuenonspecificalkalinephosphatase—a pages 1-3, sun2021mitochondrialtnapcontrols pages 4-6)
Primary molecular function: GPI-anchored, metal-dependent alkaline phosphatase/pyrophosphatase that hydrolyzes extracellular phosphate esters and PPi.
Principal physiological substrate and process: extracellular PPi at osteoblast, hypertrophic-chondrocyte and matrix-vesicle surfaces; hydrolysis increases the local Pi/PPi ratio and permits hydroxyapatite crystal growth in bone and teeth.
Additional established substrates: PLP in vitamin-B6 salvage; ATP/ADP/AMP in context-dependent extracellular nucleotide metabolism; phosphocreatine in mitochondria of brown/beige thermogenic adipocytes.
Principal locations: extracellular face of GPI-anchored plasma membrane; osteoblast/chondrocyte matrix vesicles and mineralization fronts; soluble circulating forms after anchor cleavage. A specialized GPI-linked mitochondrial inner-membrane/intermembrane-space pool occurs in mouse thermogenic adipocytes.
Evidence strength: very high for PPi-dependent skeletal/dental mineralization and PLP metabolism; high but tissue-specific for phosphocreatine thermogenesis; moderate-to-high and context dependent for purinergic nucleotide regulation; presently lower for broad proposed roles in inflammation, lipid transport and cell-fate control.
Overall, mouse Alpl/P09242 is best understood as a spatial regulator of extracellular—or, in thermogenic adipocytes, mitochondrial—phosphate chemistry. Its diverse phenotypes arise because the same catalytic core encounters different substrates in different compartments, not because it functions primarily as a conventional signaling receptor or structural protein.
References
(liedtke2020tissuenonspecificalkalinephosphatase—a pages 1-3): Daniel Liedtke, Christine Hofmann, Franz Jakob, Eva Klopocki, and Stephanie Graser. Tissue-nonspecific alkaline phosphatase—a gatekeeper of physiological conditions in health and a modulator of biological environments in disease. Dec 2020. URL: https://doi.org/10.3390/biom10121648, doi:10.3390/biom10121648. This article has 70 citations.
(buchet2013multisystemicfunctionsof pages 1-3): René Buchet, José Luis Millán, and David Magne. Multisystemic functions of alkaline phosphatases. Methods in molecular biology, 1053:27-51, Jan 2013. URL: https://doi.org/10.1007/978-1-62703-562-0_3, doi:10.1007/978-1-62703-562-0_3. This article has 254 citations and is from a peer-reviewed journal.
(buchet2013multisystemicfunctionsof pages 4-6): René Buchet, José Luis Millán, and David Magne. Multisystemic functions of alkaline phosphatases. Methods in molecular biology, 1053:27-51, Jan 2013. URL: https://doi.org/10.1007/978-1-62703-562-0_3, doi:10.1007/978-1-62703-562-0_3. This article has 254 citations and is from a peer-reviewed journal.
(buchet2013multisystemicfunctionsof pages 6-9): René Buchet, José Luis Millán, and David Magne. Multisystemic functions of alkaline phosphatases. Methods in molecular biology, 1053:27-51, Jan 2013. URL: https://doi.org/10.1007/978-1-62703-562-0_3, doi:10.1007/978-1-62703-562-0_3. This article has 254 citations and is from a peer-reviewed journal.
(orimo2010themechanismof pages 3-4): Hideo Orimo. The mechanism of mineralization and the role of alkaline phosphatase in health and disease. Journal of Nippon Medical School = Nippon Ika Daigaku zasshi, 77 1:4-12, Feb 2010. URL: https://doi.org/10.1272/jnms.77.4, doi:10.1272/jnms.77.4. This article has 1022 citations.
(sun2021mitochondrialtnapcontrols pages 2-4): Yizhi Sun, Janane F. Rahbani, Mark P. Jedrychowski, Christopher L. Riley, Sara Vidoni, Dina Bogoslavski, Bo Hu, Phillip A. Dumesic, Xing Zeng, Alex B. Wang, Nelson H. Knudsen, Caroline R. Kim, Anthony Marasciullo, José L. Millán, Edward T. Chouchani, Lawrence Kazak, and Bruce M. Spiegelman. Mitochondrial tnap controls thermogenesis by hydrolysis of phosphocreatine. Nature, 593:580-585, May 2021. URL: https://doi.org/10.1038/s41586-021-03533-z, doi:10.1038/s41586-021-03533-z. This article has 176 citations and is from a highest quality peer-reviewed journal.
(imam2024structuralandfunctional pages 15-17): Iliass Imam, Gilles Rautureau, Sébastien Violot, Eva Drevet Mulard, David Magne, and Lionel Ballut. Structural and functional integration of tissue-nonspecific alkaline phosphatase within the alkaline phosphatase superfamily: evolutionary insights and functional implications. Metabolites, 14(12):659, Nov 2024. URL: https://doi.org/10.3390/metabo14120659, doi:10.3390/metabo14120659. This article has 12 citations.
(sato2021tissuenonspecificalkalinephosphatase pages 6-8): Masahiro Sato, Issei Saitoh, Yuki Kiyokawa, Yoko Iwase, Naoko Kubota, Natsumi Ibano, Hirofumi Noguchi, Youichi Yamasaki, and Emi Inada. Tissue-nonspecific alkaline phosphatase, a possible mediator of cell maturation: towards a new paradigm. Cells, 10:3338, Nov 2021. URL: https://doi.org/10.3390/cells10123338, doi:10.3390/cells10123338. This article has 42 citations.
(sebastianserrano2016neurodevelopmentalalterationsand pages 1-2): Álvaro Sebastián-Serrano, Tobias Engel, Laura de Diego-García, Luis A. Olivos-Oré, Marina Arribas-Blázquez, Carlos Martínez-Frailes, Carmen Pérez-Díaz, José Luis Millán, Antonio R. Artalejo, María Teresa Miras-Portugal, David C. Henshall, and Miguel Díaz-Hernández. Neurodevelopmental alterations and seizures developed by mouse model of infantile hypophosphatasia are associated with purinergic signalling deregulation. Human Molecular Genetics, 25:4143-4156, Jul 2016. URL: https://doi.org/10.1093/hmg/ddw248, doi:10.1093/hmg/ddw248. This article has 82 citations and is from a domain leading peer-reviewed journal.
(sun2021mitochondrialtnapcontrols pages 4-6): Yizhi Sun, Janane F. Rahbani, Mark P. Jedrychowski, Christopher L. Riley, Sara Vidoni, Dina Bogoslavski, Bo Hu, Phillip A. Dumesic, Xing Zeng, Alex B. Wang, Nelson H. Knudsen, Caroline R. Kim, Anthony Marasciullo, José L. Millán, Edward T. Chouchani, Lawrence Kazak, and Bruce M. Spiegelman. Mitochondrial tnap controls thermogenesis by hydrolysis of phosphocreatine. Nature, 593:580-585, May 2021. URL: https://doi.org/10.1038/s41586-021-03533-z, doi:10.1038/s41586-021-03533-z. This article has 176 citations and is from a highest quality peer-reviewed journal.
(sun2021mitochondrialtnapcontrols pages 34-36): Yizhi Sun, Janane F. Rahbani, Mark P. Jedrychowski, Christopher L. Riley, Sara Vidoni, Dina Bogoslavski, Bo Hu, Phillip A. Dumesic, Xing Zeng, Alex B. Wang, Nelson H. Knudsen, Caroline R. Kim, Anthony Marasciullo, José L. Millán, Edward T. Chouchani, Lawrence Kazak, and Bruce M. Spiegelman. Mitochondrial tnap controls thermogenesis by hydrolysis of phosphocreatine. Nature, 593:580-585, May 2021. URL: https://doi.org/10.1038/s41586-021-03533-z, doi:10.1038/s41586-021-03533-z. This article has 176 citations and is from a highest quality peer-reviewed journal.
(yu2023thestructuralpathology pages 1-2): Yating Yu, Kewei Rong, Deqiang Yao, Qing Zhang, Xiankun Cao, Bing Rao, Ying Xia, Yi Lu, Yafeng Shen, Ying Yao, Hongtao Xu, Peixiang Ma, Yu Cao, and An Qin. The structural pathology for hypophosphatasia caused by malfunctional tissue non-specific alkaline phosphatase. Nature Communications, Jul 2023. URL: https://doi.org/10.1038/s41467-023-39833-3, doi:10.1038/s41467-023-39833-3. This article has 54 citations and is from a highest quality peer-reviewed journal.
(imam2024structuralandfunctional pages 1-2): Iliass Imam, Gilles Rautureau, Sébastien Violot, Eva Drevet Mulard, David Magne, and Lionel Ballut. Structural and functional integration of tissue-nonspecific alkaline phosphatase within the alkaline phosphatase superfamily: evolutionary insights and functional implications. Metabolites, 14(12):659, Nov 2024. URL: https://doi.org/10.3390/metabo14120659, doi:10.3390/metabo14120659. This article has 12 citations.
(nam2022deletionofthe pages 12-13): Hwa Kyung Nam, Emmanouil Emmanouil, and Nan E. Hatch. Deletion of the pyrophosphate generating enzyme enpp1 rescues craniofacial abnormalities in the tnap−/− mouse model of hypophosphatasia and reveals fgf23 as a marker of phenotype severity. Frontiers in dental medicine, Apr 2022. URL: https://doi.org/10.3389/fdmed.2022.846962, doi:10.3389/fdmed.2022.846962. This article has 10 citations and is from a peer-reviewed journal.
(sun2021mitochondrialtnapcontrols pages 1-2): Yizhi Sun, Janane F. Rahbani, Mark P. Jedrychowski, Christopher L. Riley, Sara Vidoni, Dina Bogoslavski, Bo Hu, Phillip A. Dumesic, Xing Zeng, Alex B. Wang, Nelson H. Knudsen, Caroline R. Kim, Anthony Marasciullo, José L. Millán, Edward T. Chouchani, Lawrence Kazak, and Bruce M. Spiegelman. Mitochondrial tnap controls thermogenesis by hydrolysis of phosphocreatine. Nature, 593:580-585, May 2021. URL: https://doi.org/10.1038/s41586-021-03533-z, doi:10.1038/s41586-021-03533-z. This article has 176 citations and is from a highest quality peer-reviewed journal.
(gasque2015improvementofthe pages 3-4): Kellen C.S. Gasque, Brian L. Foster, Pia Kuss, Manisha C. Yadav, Jin Liu, Tina Kiffer-Moreira, Andrea van Elsas, Nan Hatch, Martha J. Somerman, and José Luis Millán. Improvement of the skeletal and dental hypophosphatasia phenotype in alpl-/- mice by administration of soluble (non-targeted) chimeric alkaline phosphatase. Bone, 72:137-47, Mar 2015. URL: https://doi.org/10.1016/j.bone.2014.11.017, doi:10.1016/j.bone.2014.11.017. This article has 61 citations and is from a domain leading peer-reviewed journal.
(kinoshita2021genetherapyusing pages 1-2): Yuka Kinoshita, Fatma F Mohamed, Flavia Amadeu de Oliveira, Sonoko Narisawa, Koichi Miyake, Brian L Foster, and José Luis Millán. Gene therapy using adeno-associated virus serotype 8 encoding tnap-d10 improves the skeletal and dentoalveolar phenotypes in alpl−/− mice. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 36:1835-1849, Jun 2021. URL: https://doi.org/10.1002/jbmr.4382, doi:10.1002/jbmr.4382. This article has 64 citations.
(OpenTargets Search: -ALPL): Open Targets Query (-ALPL, 5 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.
(sato2021tissuenonspecificalkalinephosphatase pages 23-24): Masahiro Sato, Issei Saitoh, Yuki Kiyokawa, Yoko Iwase, Naoko Kubota, Natsumi Ibano, Hirofumi Noguchi, Youichi Yamasaki, and Emi Inada. Tissue-nonspecific alkaline phosphatase, a possible mediator of cell maturation: towards a new paradigm. Cells, 10:3338, Nov 2021. URL: https://doi.org/10.3390/cells10123338, doi:10.3390/cells10123338. This article has 42 citations.