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this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.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.

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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.

Comprehensive Research Report on Human ARG1 (Arginase-1, P05089)

1. Gene and Protein Identity

Human Arginase-1 (ARG1) is encoded by the ARG1 gene located on chromosome 6q23, consisting of 8 exons (nteli2024argininemiapathophysiologyand pages 8-10). The protein is classified as EC 3.5.3.1 and is also known as liver-type arginase or type I arginase (anakha2022humanarginase1 pages 1-3). ARG1 belongs to the ureohydrolase/arginase protein family and contains a characteristic ureohydrolase domain with a manganese-binding site. Over 43 pathogenic mutations have been identified in the ARG1 gene, distributed across exons and splice sites (nteli2024argininemiapathophysiologyand pages 8-10). In humans, three splice variants exist: isoform 1 (322 amino acids), mainly expressed in the liver; isoform 2 (330 amino acids), expressed in immune cells and erythrocytes; and isoform 3, whose function remains undefined (cane2025therolesof pages 1-2).

The following table summarizes key properties of ARG1:

Table: This table summarizes core biochemical, structural, localization, and disease-related properties of human Arginase-1 (ARG1/P05089). It is useful as a compact reference for functional annotation and interpretation of disease relevance.

2. Enzymatic Function and Catalytic Mechanism

2.1 Primary Reaction

ARG1 is a metalloenzyme that catalyzes the hydrolysis of L-arginine to produce L-ornithine and urea (anakha2022humanarginase1 pages 1-3, clemente2020arginaseasa pages 1-3). This reaction represents the fifth and final step of the hepatic urea cycle, completing the conversion of toxic ammonia to urea for renal excretion (nteli2024argininemiapathophysiologyand pages 2-3). The enzyme exhibits a Km of approximately 3.3 mM and a Vmax of 34 nmol·min⁻¹·mg⁻¹ at pH 7.4 (clemente2020arginaseasa pages 3-6).

2.2 Catalytic Mechanism

The catalytic mechanism of ARG1 depends on a binuclear manganese (Mn²⁺) cluster located at the active site. Two Mn²⁺ ions are positioned approximately 3.3 Å apart and are bridged by a hydroxide ion (clemente2020arginaseasa pages 1-3, palte2021cryoemstructuresof pages 1-2). During catalysis, the Mn²⁺ ions form a metal-bound hydroxide from a water molecule, which serves as the nucleophile that attacks the guanidinium carbon of L-arginine (anakha2022humanarginase1 pages 1-3, li2022reviewofarginase pages 3-5). This nucleophilic attack generates a tetrahedral intermediate that is stabilized by the binuclear Mn²⁺ center. Specific amino acid residues, including Asp128, provide stabilization through hydrogen bonding. A histidine residue (His-141 in ARG1) facilitates proton shuttling from bulk solvent to the active site, enabling L-ornithine dissociation (li2022reviewofarginase pages 3-5, clemente2020arginaseasa pages 3-6). The tetrahedral intermediate subsequently collapses to release the products L-ornithine and urea, and the metal ions recycle by rebinding water molecules for subsequent catalytic cycles (li2022reviewofarginase pages 3-5). Although Mn²⁺ is the preferred cofactor, Ni²⁺, Co²⁺, and Fe²⁺ can also activate the enzyme (li2022reviewofarginase pages 3-5).

2.3 Substrate Specificity

Wild-type human ARG1 is highly specific for L-arginine as its physiological substrate and does not efficiently hydrolyze agmatine (a decarboxylated arginine analog) (orellana2022newinsightsinto pages 1-2, orellana2022newinsightsinto pages 2-4). This specificity is determined by two critical loops at the entrance of the active site: Loop A (residues I129–L140) and Loop B (residues D181–P184) (orellana2022newinsightsinto pages 1-2). Loop A contains residues N130, S137, and N139 that specifically stabilize the α-carboxyl group of arginine through hydrogen bonding; since agmatine lacks this carboxyl group, these residues create a selectivity barrier (orellana2022newinsightsinto pages 2-4). Loop B interacts with the α-amino group of arginine and serves as a structural determinant of substrate affinity (orellana2022newinsightsinto pages 1-2, orellana2022newinsightsinto pages 11-12). Mutagenesis studies have demonstrated that engineered changes to Loop A (I129T/N130Y/T131A with deletion of P132-T134) can completely switch the enzyme's specificity from arginine to agmatine (orellana2022newinsightsinto pages 12-14, orellana2022newinsightsinto pages 6-7). Similarly, double mutations D181T/V182E in Loop B result in a 20-fold increase in Km for arginine, confirming these loops as the primary determinants of substrate recognition (orellana2022newinsightsinto pages 7-9).

3. Quaternary Structure and Assembly

ARG1 functions as an obligate homotrimer. Each monomer is approximately 35 kDa and adopts an α/β fold with a central β-sheet flanked by α-helices (clemente2020arginaseasa pages 3-6, palte2021cryoemstructuresof pages 1-2). The trimeric complex has a total molecular weight of approximately 105–130 kDa, depending on the construct and measurement method (anakha2022humanarginase1 pages 1-3, li2022reviewofarginase pages 3-5). Each monomer contains a separate active site with its own binuclear Mn²⁺ center (li2022reviewofarginase pages 3-5).

Critically, only the trimeric form of ARG1 is catalytically active. Production of a monomeric form results in greater than 90% loss of enzymatic activity (dechenne2025examiningarginase1trimerization pages 7-9, dechenne2025examiningarginase1trimerization pages 1-2). The trimeric interface involves two α-helices and a C-terminal tail, with five key amino acids (M200, D204, R255, E256, R308) being essential for trimerization. Mutation of R255 to alanine produces a fully monomeric, inactive enzyme (dechenne2025examiningarginase1trimerization pages 7-9, dechenne2025examiningarginase1trimerization pages 2-5). The active site extends approximately 15 Å deep and terminates at the two catalytic manganese ions (palte2021cryoemstructuresof pages 1-2). This structural dependence on trimerization has been exploited as a novel drug target—phenylglyoxal covalently modifies a critical arginine residue (R205) within the allosteric trimerization pocket, disrupting oligomerization and partially reducing enzymatic activity (dechenne2025examiningarginase1trimerization pages 9-10, dechenne2025examiningarginase1trimerization pages 1-2). Cryo-EM structures of inhibitory antibodies complexed with ARG1 have been resolved at local resolutions of 3.5 Å or better, revealing both orthosteric and allosteric mechanisms of inhibition (palte2021cryoemstructuresof pages 1-2).

4. Subcellular Localization and Tissue Distribution

ARG1 is a cytosolic enzyme, in contrast to arginase 2 (ARG2), which localizes to the mitochondrial matrix (clemente2020arginaseasa pages 1-3, anakha2022humanarginase1 pages 1-3, cane2025therolesof pages 2-3). Its primary site of expression is the liver, where it is highly expressed in periportal (zone 1) hepatocytes—the region where blood arriving via the portal vein is rich in oxygen and amino acids, and where urea cycle enzymes are most active for ammonia detoxification (zhu2026ureacycledysregulation pages 4-5). Beyond the liver, ARG1 is also detected in erythrocytes, vascular endothelial cells, and immune cells, including M2-polarized macrophages, neutrophils, and myeloid-derived suppressor cells (MDSCs) (nteli2024argininemiapathophysiologyand pages 2-3, cane2025therolesof pages 1-2, cane2025therolesof pages 2-3). Neutrophils store ARG1 in gelatinase (tertiary) granules, from which it can be released upon degranulation (nteli2024argininemiapathophysiologyand pages 2-3).

5. Biochemical Pathways

5.1 The Urea Cycle

In hepatocytes, ARG1 catalyzes the final step of the urea cycle by hydrolyzing L-arginine to L-ornithine and urea. The ornithine product is recycled into the urea cycle via ornithine transcarbamylase (OTC) in the mitochondria, while urea is transported through the bloodstream to the kidneys for excretion (nteli2024argininemiapathophysiologyand pages 2-3, clemente2020arginaseasa pages 1-3). This pathway is the primary route for nitrogen disposal in mammals, converting highly toxic ammonia to the relatively benign molecule urea.

5.2 Downstream Metabolic Pathways

The L-ornithine produced by ARG1 serves as a critical metabolic branch-point feeding into two major downstream pathways, summarized in the following table:

Table: This table summarizes the main biochemical fates of ARG1-generated ornithine and the competing NOS branch from arginine. It is useful for understanding how ARG1 links the urea cycle to polyamine synthesis, proline/collagen production, and nitric-oxide-related signaling.

First, L-ornithine enters the polyamine synthesis pathway, where ornithine decarboxylase (ODC/ODC1) converts it to putrescine in the rate-limiting first step. Putrescine is then sequentially converted to spermidine by spermidine synthase (SRM) and to spermine by spermine synthase (SMS). These polyamines are essential for cell proliferation, migration, epigenetic regulation, and differentiation (li2026arg1polyamineaxiscelltypespecific pages 1-2, cane2025therolesof pages 2-3, li2026arg1polyamineaxiscelltypespecific pages 2-3).

Second, L-ornithine can be transaminated by ornithine aminotransferase (OAT) to produce L-glutamate 5-semialdehyde, which is further converted to 1-pyrroline-5-carboxylate (P5C) and then to L-proline by pyrroline-5-carboxylate reductase (PYCR). Proline is a critical building block for collagen and extracellular matrix deposition, linking ARG1 activity to tissue repair and fibrosis (cane2025therolesof pages 2-3, karadima2025argininemetabolismin pages 1-2).

5.3 Competition with Nitric Oxide Synthase

A critically important aspect of ARG1 biology is its competition with nitric oxide synthase (NOS) for the shared substrate L-arginine (li2026arg1polyamineaxiscelltypespecific pages 1-2, li2026arg1polyamineaxiscelltypespecific pages 2-3). While ARG1 hydrolyzes L-arginine to ornithine and urea, NOS enzymes (iNOS, eNOS, nNOS) oxidize L-arginine to produce nitric oxide (NO) and citrulline. Although NOS has a higher substrate affinity (lower Km), ARG1 possesses a 10³–10⁴ times higher Vmax, making it a highly effective competitor that can deplete the L-arginine pool available for NO production (clemente2020arginaseasa pages 3-6). This competition has multiple downstream consequences: decreased L-arginine availability for NOS, potential uncoupling of NOS to produce harmful superoxide and peroxynitrite, and repression of NOS2 protein translation and stability (cane2025therolesof pages 2-3). The balance between the ARG1 and NOS pathways fundamentally determines whether cellular arginine metabolism favors immune suppression and tissue repair (via ornithine/polyamines/proline) or pro-inflammatory/antimicrobial responses (via NO) (li2026arg1polyamineaxiscelltypespecific pages 1-2, li2026arg1polyamineaxiscelltypespecific pages 2-3, karadima2025argininemetabolismin pages 1-2).

6. Role in Immune Regulation

6.1 Macrophage Polarization

ARG1 is a defining marker and functional effector of M2 (alternatively activated, anti-inflammatory) macrophages. Its expression is induced by T helper 2 (Th2) cytokines IL-4 and IL-13 through JAK-STAT6 signaling, and by anti-inflammatory cytokines IL-10 and TGFβ. Pro-inflammatory cytokines IL-6 and TNF can also upregulate ARG1 through STAT3-dependent mechanisms (li2026arg1polyamineaxiscelltypespecific pages 4-5, pan2025harnessingaminoacid pages 8-10, cane2025therolesof pages 3-4). In macrophages, ARG1-derived ornithine fuels polyamine synthesis via ODC, promoting M2 polarization through enhanced mitochondrial oxidative phosphorylation, epigenetic modifications, autophagy, and efferocytosis (li2026arg1polyamineaxiscelltypespecific pages 4-5, pan2025harnessingaminoacid pages 8-10, li2026arg1polyamineaxiscelltypespecific pages 2-3). The ARG1/iNOS competitive axis represents a metabolic switch: in M1 pro-inflammatory macrophages, iNOS predominates to produce NO, whereas in M2 macrophages, ARG1 predominates to produce ornithine and polyamines (li2026arg1polyamineaxiscelltypespecific pages 5-7).

6.2 T Cell Suppression

Myeloid cell-derived ARG1 represents a major immunosuppressive mechanism. By depleting extracellular L-arginine, ARG1 impairs T cell activation and proliferation through downregulation of the T cell receptor CD3ζ chain (pan2025harnessingaminoacid pages 8-10, grzybowski2025metabolomicreprogrammingof pages 2-3). This mechanism is operative in tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), and tumor-associated neutrophils (TANs), all of which upregulate ARG1 to create an immunosuppressive tumor microenvironment (li2026arg1polyamineaxiscelltypespecific pages 4-5, li2026arg1polyamineaxiscelltypespecific pages 5-7, li2026arg1polyamineaxiscelltypespecific pages 3-4, cane2025therolesof pages 17-17). In pancreatic cancer, genetic inactivation of ARG1 in macrophages delays formation of invasive disease while increasing CD8⁺ T cell infiltration, directly demonstrating that ARG1 functions as more than a mere polarization marker—it actively drives immune suppression (li2026arg1polyamineaxiscelltypespecific pages 3-4). Lactic acid in the tumor microenvironment further induces ARG1 expression in TAMs via hypoxia-inducible factor stabilization (cane2025therolesof pages 3-4).

7. Disease Associations

7.1 Argininemia (Arginase Deficiency)

Loss-of-function mutations in ARG1 cause argininemia (arginase-1 deficiency, OMIM), a rare autosomal recessive urea cycle disorder (anakha2022humanarginase1 pages 1-3, nteli2024argininemiapathophysiologyand pages 2-3). The disease is characterized by severely elevated plasma arginine (>300 µmol/L) and erythrocyte arginase activity below 1% of normal (nteli2024argininemiapathophysiologyand pages 5-7). Clinical manifestations include progressive spastic diplegia/paraparesis (the hallmark symptom beginning in the first decade of life), cognitive deficits, intellectual disability, seizures (in 60–75% of patients), and hepatic dysfunction ranging from neonatal jaundice to cirrhosis (nteli2024argininemiapathophysiologyand pages 2-3). The pathophysiology involves direct neurotoxicity of elevated arginine, accumulation of neurotoxic and epileptogenic guanidino compounds, excessive NO production leading to endothelial abnormalities, and decreased ornithine levels impairing oligodendrocyte function and causing dysmyelination (nteli2024argininemiapathophysiologyand pages 3-5). Current treatments include dietary protein restriction with essential amino acid supplementation, nitrogen scavengers (benzoate, phenylbutyrate), and liver transplantation, which effectively normalizes arginine and ammonia levels (nteli2024argininemiapathophysiologyand pages 5-7). Pegzilarginase (Co-rhARG1-PEG), a PEGylated cobalt-substituted recombinant human arginase 1 with improved stability and half-life, has received FDA Breakthrough Therapy Designation and has shown efficacy in reducing plasma arginine in approximately 50% of patients (anakha2022humanarginase1 pages 3-4). OpenTargets data confirms strong disease-target associations between ARG1 and arginase deficiency (score 0.78) and argininemia (score 0.80), as well as associations with hereditary disease (score 0.86), type 2 diabetes mellitus (score 0.44), and obesity disorder (score 0.36) (OpenTargets Search: -ARG1).

7.2 Cancer and Immunotherapy

ARG1 is increasingly recognized as a therapeutic target in cancer immunotherapy. Elevated ARG1 activity in the tumor microenvironment correlates with poor prognosis across multiple cancer types by promoting immune evasion through L-arginine depletion and polyamine-mediated tumor cell proliferation (grzybowski2025metabolomicreprogrammingof pages 2-3). The arginase inhibitor CB-1158 (INCB001158/numidargistat), with an IC₅₀ of 98 nM for ARG1, was evaluated in a first-in-human phase 1 clinical trial (NCT02903914) in patients with advanced solid tumors. While generally well tolerated and showing pharmacodynamic activity (dose-dependent increases in plasma arginine), the limited antitumor activity observed as monotherapy or in combination with pembrolizumab suggested that the role of arginine depletion in cancer is multifaceted (marzetaassas2024pathophysiologyofarginases pages 13-14, marzetaassas2024pathophysiologyofarginases pages 11-13). A key limitation of CB-1158 is its restricted intracellular penetration, affecting primarily extracellular ARG1 (grzybowski2025metabolomicreprogrammingof pages 2-3). The next-generation dual ARG1/ARG2 inhibitor OATD-02 (IC₅₀ 20–48 nM) was designed to overcome this limitation by effectively inhibiting both extracellular and intracellular arginases (marzetaassas2024pathophysiologyofarginases pages 13-14, borek2023arginase12inhibitor pages 1-1). Preclinical studies show that OATD-02 restores intratumoral L-arginine while depleting polyamines, leading to increased CD8⁺ T cell infiltration, enhanced T cell activation, and improved response to anti-PD-1 checkpoint blockade (grzybowski2025metabolomicreprogrammingof pages 1-2). OATD-02 is currently undergoing clinical evaluation in a phase I/II trial (NCT05759923) (grzybowski2025metabolomicreprogrammingof pages 1-2).

8. Summary

Human ARG1 is a cytosolic, homotrimeric, binuclear manganese metalloenzyme that catalyzes the final step of the urea cycle—the hydrolysis of L-arginine to L-ornithine and urea. Its enzymatic activity is strictly dependent on trimeric assembly and the presence of two Mn²⁺ ions at each active site. The enzyme is highly specific for L-arginine, with substrate recognition determined by two structural loops (Loop A and Loop B) at the active site entrance. ARG1 is predominantly expressed in liver periportal hepatocytes, where it functions in nitrogen detoxification, but is also expressed in immune cells (M2 macrophages, MDSCs, neutrophils), where it serves as a key immunomodulatory enzyme. Through competition with NOS for L-arginine and through production of ornithine-derived polyamines and proline, ARG1 occupies a critical metabolic branch-point linking nitrogen metabolism, immune regulation, tissue repair, and cell proliferation. Loss of ARG1 function causes the rare metabolic disorder argininemia, while overexpression in the tumor microenvironment contributes to immune evasion in cancer, making ARG1 an active target for both enzyme replacement therapy and immunotherapeutic inhibition.

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21. (orellana2022newinsightsinto pages 11-12): María-Soledad Orellana, Gonzalo A. Jaña, Maximiliano Figueroa, José Martínez-Oyanedel, Fabiola E. Medina, Estefanía Tarifeño-Saldivia, Marcell Gatica, María Ángeles García-Robles, Nelson Carvajal, and Elena Uribe. New insights into the determinants of specificity in human type i arginase: generation of a mutant that is only active with agmatine as substrate. International Journal of Molecular Sciences, 23:6438, Jun 2022. URL: https://doi.org/10.3390/ijms23126438, doi:10.3390/ijms23126438. This article has 2 citations.

22. (orellana2022newinsightsinto pages 12-14): María-Soledad Orellana, Gonzalo A. Jaña, Maximiliano Figueroa, José Martínez-Oyanedel, Fabiola E. Medina, Estefanía Tarifeño-Saldivia, Marcell Gatica, María Ángeles García-Robles, Nelson Carvajal, and Elena Uribe. New insights into the determinants of specificity in human type i arginase: generation of a mutant that is only active with agmatine as substrate. International Journal of Molecular Sciences, 23:6438, Jun 2022. URL: https://doi.org/10.3390/ijms23126438, doi:10.3390/ijms23126438. This article has 2 citations.

23. (orellana2022newinsightsinto pages 7-9): María-Soledad Orellana, Gonzalo A. Jaña, Maximiliano Figueroa, José Martínez-Oyanedel, Fabiola E. Medina, Estefanía Tarifeño-Saldivia, Marcell Gatica, María Ángeles García-Robles, Nelson Carvajal, and Elena Uribe. New insights into the determinants of specificity in human type i arginase: generation of a mutant that is only active with agmatine as substrate. International Journal of Molecular Sciences, 23:6438, Jun 2022. URL: https://doi.org/10.3390/ijms23126438, doi:10.3390/ijms23126438. This article has 2 citations.

24. (dechenne2025examiningarginase1trimerization pages 2-5): Juhans Dechenne, Magdalena Wierzbicka, Reda Krimou, Asia El Aakchioui, Julia Malo Pueyo, Joris Messens, Marianne Fillet, Quentin Spillier, and Raphaël Frédérick. Examining arginase-1 trimerization uncovers a promising allosteric site for inhibition. Journal of medicinal chemistry, 68:1433-1445, Jan 2025. URL: https://doi.org/10.1021/acs.jmedchem.4c01993, doi:10.1021/acs.jmedchem.4c01993. This article has 3 citations and is from a highest quality peer-reviewed journal.

25. (dechenne2025examiningarginase1trimerization pages 9-10): Juhans Dechenne, Magdalena Wierzbicka, Reda Krimou, Asia El Aakchioui, Julia Malo Pueyo, Joris Messens, Marianne Fillet, Quentin Spillier, and Raphaël Frédérick. Examining arginase-1 trimerization uncovers a promising allosteric site for inhibition. Journal of medicinal chemistry, 68:1433-1445, Jan 2025. URL: https://doi.org/10.1021/acs.jmedchem.4c01993, doi:10.1021/acs.jmedchem.4c01993. This article has 3 citations and is from a highest quality peer-reviewed journal.

26. (li2026arg1polyamineaxiscelltypespecific pages 1-2): Lexing Li, Guoyan Zhu, Meng-Zhang Chen, Bingqing Qiu, Yujia Li, Shiyu Liu, Wei Gu, and Leilei Liu. Arg1-polyamine axis: cell-type-specific functions in disease pathogenesis and therapeutic targeting. Frontiers in Immunology, Mar 2026. URL: https://doi.org/10.3389/fimmu.2026.1744890, doi:10.3389/fimmu.2026.1744890. This article has 0 citations and is from a peer-reviewed journal.

27. (li2026arg1polyamineaxiscelltypespecific pages 2-3): Lexing Li, Guoyan Zhu, Meng-Zhang Chen, Bingqing Qiu, Yujia Li, Shiyu Liu, Wei Gu, and Leilei Liu. Arg1-polyamine axis: cell-type-specific functions in disease pathogenesis and therapeutic targeting. Frontiers in Immunology, Mar 2026. URL: https://doi.org/10.3389/fimmu.2026.1744890, doi:10.3389/fimmu.2026.1744890. This article has 0 citations and is from a peer-reviewed journal.

28. (xu2026molecularmechanismsand pages 3-4): Yuhang Xu, Mingxin Yu, Yi Zhang, Yiqing Jiang, Haiyan Zhu, Shujuan He, Guohua Yu, Niannian Li, Shuzhen Liu, and Bin Liu. Molecular mechanisms and therapies for tumor inhibition through the arginine metabolism pathway. Frontiers in Oncology, Feb 2026. URL: https://doi.org/10.3389/fonc.2026.1774392, doi:10.3389/fonc.2026.1774392. This article has 0 citations.

29. (karadima2025argininemetabolismin pages 1-2): Eleftheria Karadima, Triantafyllos Chavakis, and Vasileia Ismini Alexaki. Arginine metabolism in myeloid cells in health and disease. Seminars in Immunopathology, Jan 2025. URL: https://doi.org/10.1007/s00281-025-01038-9, doi:10.1007/s00281-025-01038-9. This article has 67 citations and is from a domain leading peer-reviewed journal.

30. (li2026arg1polyamineaxiscelltypespecific pages 4-5): Lexing Li, Guoyan Zhu, Meng-Zhang Chen, Bingqing Qiu, Yujia Li, Shiyu Liu, Wei Gu, and Leilei Liu. Arg1-polyamine axis: cell-type-specific functions in disease pathogenesis and therapeutic targeting. Frontiers in Immunology, Mar 2026. URL: https://doi.org/10.3389/fimmu.2026.1744890, doi:10.3389/fimmu.2026.1744890. This article has 0 citations and is from a peer-reviewed journal.

31. (pan2025harnessingaminoacid pages 8-10): Jiongli Pan, Yi Lin, Xinyuan Liu, Xiaozhen Zhang, Tingbo Liang, and Xueli Bai. Harnessing amino acid pathways to influence myeloid cell function in tumor immunity. Molecular Medicine, Feb 2025. URL: https://doi.org/10.1186/s10020-025-01099-4, doi:10.1186/s10020-025-01099-4. This article has 18 citations and is from a peer-reviewed journal.

32. (cane2025therolesof pages 3-4): Stefania Canè, Roger Geiger, and Vincenzo Bronte. The roles of arginases and arginine in immunity. Nature reviews. Immunology, Oct 2025. URL: https://doi.org/10.1038/s41577-024-01098-2, doi:10.1038/s41577-024-01098-2. This article has 118 citations.

33. (li2026arg1polyamineaxiscelltypespecific pages 5-7): Lexing Li, Guoyan Zhu, Meng-Zhang Chen, Bingqing Qiu, Yujia Li, Shiyu Liu, Wei Gu, and Leilei Liu. Arg1-polyamine axis: cell-type-specific functions in disease pathogenesis and therapeutic targeting. Frontiers in Immunology, Mar 2026. URL: https://doi.org/10.3389/fimmu.2026.1744890, doi:10.3389/fimmu.2026.1744890. This article has 0 citations and is from a peer-reviewed journal.

34. (li2026arg1polyamineaxiscelltypespecific pages 3-4): Lexing Li, Guoyan Zhu, Meng-Zhang Chen, Bingqing Qiu, Yujia Li, Shiyu Liu, Wei Gu, and Leilei Liu. Arg1-polyamine axis: cell-type-specific functions in disease pathogenesis and therapeutic targeting. Frontiers in Immunology, Mar 2026. URL: https://doi.org/10.3389/fimmu.2026.1744890, doi:10.3389/fimmu.2026.1744890. This article has 0 citations and is from a peer-reviewed journal.

35. (cane2025therolesof pages 17-17): Stefania Canè, Roger Geiger, and Vincenzo Bronte. The roles of arginases and arginine in immunity. Nature reviews. Immunology, Oct 2025. URL: https://doi.org/10.1038/s41577-024-01098-2, doi:10.1038/s41577-024-01098-2. This article has 118 citations.

36. (nteli2024argininemiapathophysiologyand pages 3-5): Despoina Nteli, Maria Nteli, Konstantinos Konstantinidis, Anastasia Foka, Foteini Charisi, Iliana Michailidou, Sotiria Stavropoulou De Lorenzo, Marina Boziki, Maria Tzitiridou-Chatzopoulou, Evangelia Spandou, Constantina Simeonidou, Christos Bakirtzis, and Evangelia Kesidou. Argininemia: pathophysiology and novel methods for evaluation of the disease. Applied Sciences, 14:1647, Feb 2024. URL: https://doi.org/10.3390/app14041647, doi:10.3390/app14041647. This article has 4 citations.

37. (marzetaassas2024pathophysiologyofarginases pages 11-13): Patrycja Marzęta-Assas, Damian Jacenik, and Zbigniew Zasłona. Pathophysiology of arginases in cancer and efforts in their pharmacological inhibition. International Journal of Molecular Sciences, 25:9782, Sep 2024. URL: https://doi.org/10.3390/ijms25189782, doi:10.3390/ijms25189782. This article has 17 citations.

38. (borek2023arginase12inhibitor pages 1-1): Bartlomiej Borek, Julita Nowicka, Anna Gzik, Marek Dziegielewski, Karol Jedrzejczak, Joanna Brzezinska, Marcin Grzybowski, Paulina Stanczak, Paulina Pomper, Agnieszka Zagozdzon, Tomasz Rejczak, Krzysztof Matyszewski, Adam Golebiowski, Jacek Olczak, Kamil Lisiecki, Magdalena Tyszkiewicz, Magdalena Kania, Sylwia Piasecka, Anna Cabaj, Paulina Dera, Krzysztof Mulewski, Jacek Chrzanowski, Damian Kusmirek, Elzbieta Sobolewska, Marta Magdycz, Lukasz Mucha, Marek Masnyk, Jakub Golab, Marcin Nowotny, Elzbieta Nowak, Agnieszka Napiorkowska-Gromadzka, Stanislaw Pikul, Radoslaw Jazwiec, Karolina Dzwonek, Pawel Dobrzanski, Michael Meyring, Krzysztof Skowronek, Piotr Iwanowski, Zbigniew Zaslona, and Roman Blaszczyk. Arginase 1/2 inhibitor oatd-02: from discovery to first-in-man setup in cancer immunotherapy. Molecular cancer therapeutics, 22:807-817, Mar 2023. URL: https://doi.org/10.1158/1535-7163.mct-22-0721, doi:10.1158/1535-7163.mct-22-0721. This article has 37 citations and is from a peer-reviewed journal.

39. (grzybowski2025metabolomicreprogrammingof pages 1-2): Marcin Mikołaj Grzybowski, Yasemin Uçal, Angelika Muchowicz, Tomasz Rejczak, Agnieszka Kikulska, Katarzyna Maria Głuchowska, Małgorzata Szostakowska-Rodzoś, Agnieszka Zagożdżon, Tobias Bausbacher, Agnieszka Tkaczyk, Magdalena Kulma, Paulina Pomper, Michał Mlącki, Adam Konrad Jagielski, Roman Błaszczyk, Carsten Hopf, and Zbigniew Zasłona. Metabolomic reprogramming of the tumor microenvironment by dual arginase inhibitor oatd-02 boosts anticancer immunity. Scientific Reports, May 2025. URL: https://doi.org/10.1038/s41598-025-03446-1, doi:10.1038/s41598-025-03446-1. This article has 24 citations and is from a peer-reviewed journal.

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Citations

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