{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nProtein tyrosine phosphatase non‐receptor type 21 (PTPN21), which in several reports is also referred to as PTPD1, acts as a versatile regulator of cell signalling by integrating cues from the actin cytoskeleton and adhesion complexes. Studies have shown that its FERM domain drives membrane targeting and assembly into multiprotein complexes at cell adhesions, where it modulates Src–EGF receptor (EGFR)–FAK signalling and thereby promotes processes such as cell scattering, adhesion and migration."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in adhesion dynamics, PTPN21 regulates intracellular transport. The phosphatase releases autoinhibition of the kinesin‐3 motor KIF1C by binding to its stalk region, thereby facilitating the motor’s attachment to microtubules and promoting efficient cargo transport. This regulation of motor activity is essential for the trafficking of integrins to adhesion sites and the directed delivery of dense core vesicles in neurons."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMore broadly, perturbations in the balanced activity of protein tyrosine phosphatases have been implicated in tumorigenesis. Comprehensive mutational analyses of the PTP family underscore the significance of these phosphatases in controlling proliferation and differentiation, with aberrations contributing to various malignancies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic studies have further linked PTPN21 to neuropsychiatric and autoimmune conditions. Genome‐wide association analyses have identified non‐synonymous variants in PTPN21 that are associated with an altered risk for schizophrenia, and its genomic locus has been investigated as a candidate susceptibility region in Graves’ disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of oncogenesis, PTPN21 has emerged as a factor with context‐dependent roles. Molecular investigations revealed that while PTPN21 can engage viral oncoproteins such as HPV18 E7 in a manner analogous to its tumor‐suppressive homolog PTPN14, the biological outcome differs; specifically, PTPN21 is spared from degradation and instead contributes to enhanced cell migration and invasion. Moreover, in acute lymphoblastic leukemia (ALL), differential expression of its isoforms appears to influence immune evasion and proliferation: knockout of the longer isoform heightened NK cell–mediated killing by downregulating HLA class I molecules, and excessive PTPN21 activity in ALL cells has been linked to proliferation in response to EGF stimulation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Annalisa Carlucci, Chiara Gedressi, Luca Lignitto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Protein-tyrosine phosphatase PTPD1 regulates focal adhesion kinase autophosphorylation and cell migration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M707248200"}], "href": "https://doi.org/10.1074/jbc.M707248200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18223254"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18223254"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Annalisa Carlucci, Monia Porpora, Corrado Garbi, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "PTPN21 and Hook3 relieve KIF1C autoinhibition and activate intracellular transport."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-019-10644-9"}], "href": "https://doi.org/10.1038/s41467-019-10644-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31217419"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31217419"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Sebastian Korff, Stefan M Woerner, Yan P Yuan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Frameshift mutations in coding repeats of protein tyrosine phosphatase genes in colorectal tumors with microsatellite instability."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Cancer (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1471-2407-8-329"}], "href": "https://doi.org/10.1186/1471-2407-8-329"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19000305"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19000305"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jingchun Chen, Grace Lee, Ayman H Fanous, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Two non-synonymous markers in PTPN21, identified by genome-wide association study data-mining and replication, are associated with schizophrenia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Schizophr Res (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.schres.2011.06.023"}], "href": "https://doi.org/10.1016/j.schres.2011.06.023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21752600"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21752600"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "A A Zeitlin, J M Heward, O J Brand, et al. 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