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Emphasis is placed on its cell-type-specific expression across neurons, astrocytes, microglia, and oligodendrocytes, and how this expression dynamically shifts under pathological contexts such as Parkinson\u2019s disease, stroke, and demyelinating disorders. GPR37 modulates neuroinflammatory responses, apoptosis, and oxidative stress through context-dependent mechanisms shaped by its ligands, including prosaposin, neuroprotectin D1, and osteocalcin. Additionally, GPR37 dysfunction\u2013especially via receptor misfolding and ER stress\u2013contributes to neuronal vulnerability. We further discuss its emerging role as a pharmacological target and potential biomarker in CNS disorders. By integrating findings across molecular, cellular, and disease models, we propose a context-dependent framework positioning GPR37 as a multifunctional regulator and therapeutic candidate in neurodegeneration.<\/jats:p>","DOI":"10.3389\/fncel.2025.1617682","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T05:38:35Z","timestamp":1753940315000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Role and regulatory mechanism of GPR37 in neurological diseases"],"prefix":"10.3389","volume":"19","author":[{"given":"Shuo","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwen","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Sui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1590\/0004-282x20200018","article-title":"Neurological diseases in Peru: A systematic analysis of the global burden disease study.","volume":"78","author":"Alva-D\u00edaz","year":"2020","journal-title":"Arq. 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