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Disruptions in this pathway underlie multiple visual disorders in humans. TMEM24\/C2CD2L, an SMP domain\u2010containing phospholipid transporter enriched at endoplasmic reticulum (ER)\u2010plasma membrane (PM) contact sites, regulates phosphoinositide homeostasis and calcium signaling. However, its role in the retina remains unknown. Here, we show that C2CD2L is predominantly expressed in retinal photoreceptors. Using a rod\u2010specific conditional knockout mouse, we demonstrate that loss of C2CD2L impairs rod\u2010mediated visual function, causes progressive outer retinal degeneration, induces reactive M\u00fcller glia activation, and triggers apoptotic photoreceptor death. Transcriptomic profiling of pre\u2010degenerative retinas revealed significant downregulation of genes associated with voltage\u2010gated calcium channel complexes, postsynaptic density membranes, and visual perception. These changes were accompanied by severe synaptic defects, including fewer RIBEYE\u2010 and Bassoon\u2010positive puncta, reduced ribbon\u2010bearing terminals, shortened synaptic ribbons, and decreased ribbon\u2010tethered synaptic vesicles. Our findings establish C2CD2L as a critical regulator of rod photoreceptor synaptic integrity, calcium\u2010channel\u2010associated signaling, and retinal homeostasis.<\/jats:p>","DOI":"10.1096\/fj.202602920rr","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T07:18:49Z","timestamp":1791962329000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lipid Transporter\n                    <scp>TMEM24<\/scp>\n                    \/\n                    <scp>C2CD2L<\/scp>\n                    Plays Essential Roles in Retinal Photoreceptor Survival by Regulating Calcium Signaling and Synaptic Transmission"],"prefix":"10.1096","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0652-5385","authenticated-orcid":false,"given":"Guangyi","family":"Chen","sequence":"first","affiliation":[{"name":"Genetic Diseases Key Laboratory of Sichuan Province, Department of Medical Genetics, 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