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Spontaneous near\u2010membrane Ca\n                    <jats:sup>2+<\/jats:sup>\n                    microdomains (smCa) have been identified in sensory neurons, yet their molecular origin and functional role in repair remain unclear. Here, by resolving Ca\n                    <jats:sup>2+<\/jats:sup>\n                    dynamics at sub\u2010cellular resolution, we show that TRPC3 drives smCa hotspots, which function as a localized signaling module that avoids global toxicity to instruct repair. Using peripheral sensory neurons as a primary model, we show that TRPC3\u2010smCa constitutes a basic instructive unit that appears both necessary and sufficient to initiate axon regeneration, a process that involves calmodulin\u2010dependent pathways. Following sciatic nerve injury, TRPC3\u2010smCa axis is essential for structural and functional recovery. Our data further suggest that this repair module also operates in\u00a0central nervous system: in midbrain dopaminergic neurons, TRPC3\u2010smCa is associated with a neuroprotective state, correlating with enhanced neuronal survival and motor function in a Parkinson's disease model. This pro\u2010repair correlation is further observed in human ESC\u2010derived dopaminergic neurons. Collectively, our findings identify TRPC3\u2010driven Ca\n                    <jats:sup>2+<\/jats:sup>\n                    microdomains as a repair module, pointing to a spatial logic for neural repair with potential relevance for nerve injury and neurodegenerative disorders.\n                  <\/jats:p>","DOI":"10.1002\/advs.77156","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T12:46:53Z","timestamp":1787662013000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["TRPC3\u2010Driven Calcium Microdomains Instruct Peripheral Nerve Regeneration With Protective Implications for Central Neurons"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-3842-8349","authenticated-orcid":false,"given":"Yu","family":"Lu","sequence":"first","affiliation":[{"name":"Neuroscience Research Center Key Laboratory of Biomedical Information Engineering of Ministry of 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