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Alternative inclusion of the Ig\u2010domain mini\u2010exons meA and meB tailors the ectodomain surface, thereby dictating high\u2010affinity engagement with IL1RAPL1, IL1RAP, Slitrks, LRFN4\/5 (SALM3\/5), neuroligin\u20103, and other postsynaptic partners. Intracellularly, the catalytically active D1 domain and scaffold\u2010like D2 module, anchored to liprin\u2010\u03b1, coordinate presynaptic vesicle release, postsynaptic receptor composition, and synaptic plasticity. Beyond synapses, PTPRD restrains embryonic neurogenesis, promotes STAT3\u2010dependent gliogenesis, accelerates oligodendrocyte myelination, and guides Sema3a\/Fyn\u2010mediated axon and dendrite patterning. In the adult brain it serves as the high\u2010affinity hypothalamic and cerebellar receptor for asprosin, thereby coupling systemic energy and hydration states to feeding and drinking behavior. Human genetic studies and mouse models link these molecular activities to a spectrum of conditions\u2014including restless legs syndrome, addiction, Alzheimer's disease, ADHD, OCD, autism spectrum disorder, and metabolic syndrome. Because PTPRD functions are pathway\u2010specific and shaped by mini\u2010exon usage or redundancy with other family members (PTPRS\/PTPRF), domain\u2010 or ligand\u2010selective interventions represent plausible therapeutic strategies. Elucidating its full ligand repertoire, substrate landscape, and structural basis for allosteric regulation will be critical for converting this versatile receptor from a mechanistic curiosity into a tractable target for neurodevelopmental, neuropsychiatric, and metabolic disorders.<\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70292-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70292","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T09:42:10Z","timestamp":1762767730000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Synaptic and Non\u2010Synaptic Functions of\n                    <scp>PTPRD<\/scp>\n                    : A Receptor Tyrosine Phosphatase at the Crossroads of Neural Circuitry and Metabolism"],"prefix":"10.1111","volume":"169","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0231-6055","authenticated-orcid":false,"given":"Seoyeong","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Biological Sciences Korea Advanced Institute for Science and Technology (KAIST)  Daejeon Korea"},{"name":"Center for Synaptic Brain Dysfunctions Institute for Basic Science (IBS)  Daejeon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae 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