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While several lipid transfer proteins (LTPs) are localized at MCS, their physiological significance is poorly understood. Ceramide transfer protein (CERT) transfers ceramide between membranes in vitro. However, evidence for the in vivo significance of CERT function is limited. We find that loss of dcert, the only gene encoding CERT in Drosophila, results in elevated levels of short-chain ceramides along with reductions in the levels of its metabolite phosphoethanolamine ceramide in photoreceptors. Physiological analysis showed a reduced electrical response to light stimulation in dcert mutants. dcert mutants showed a reduction in the rate of phosphatidylinositol 4,5-bisphosphate (PIP2) resynthesis following light-induced phospholipase C (PLC) stimulation, associated with reduced ER-plasma membrane MCS density and function of the MCS-localized protein RDGB. Together, our findings suggest that CERT function regulates G-protein\u2013coupled PLC signalling through modulation of MCS function in vivo.<\/jats:p>","DOI":"10.1083\/jcb.202511193","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T06:21:04Z","timestamp":1785392464000},"update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Ceramide transfer protein regulates G-protein\u2013coupled phospholipase signalling in photoreceptors"],"prefix":"10.1083","volume":"225","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7915-8297","authenticated-orcid":true,"given":"Shirish","family":"Mishra","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03gf8rp76","id-type":"ROR","asserted-by":"publisher"}],"name":"National Centre for Biological Sciences-TIFR, GKVK Campus 1 , Bangalore,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7726-8409","authenticated-orcid":true,"given":"Ali","family":"Khan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02n9z0v62","id-type":"ROR","asserted-by":"publisher"}],"name":"Amity Institute of Integrative Sciences and Health, Amity University Haryana 2 , Gurgaon,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0245-1855","authenticated-orcid":true,"given":"Vaisaly R.","family":"Nath","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03gf8rp76","id-type":"ROR","asserted-by":"publisher"}],"name":"National Centre for Biological Sciences-TIFR, GKVK Campus 1 , Bangalore,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2528-8702","authenticated-orcid":true,"given":"Tejaswini","family":"Manoj","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03gf8rp76","id-type":"ROR","asserted-by":"publisher"}],"name":"National Centre for Biological Sciences-TIFR, GKVK Campus 1 , Bangalore,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5422-7760","authenticated-orcid":true,"given":"Thejaswini","family":"Balavali Gangadhar","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03gf8rp76","id-type":"ROR","asserted-by":"publisher"}],"name":"National Centre for Biological Sciences-TIFR, GKVK Campus 1 , Bangalore,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3949-9588","authenticated-orcid":true,"given":"Preethi","family":"Alex","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03gf8rp76","id-type":"ROR","asserted-by":"publisher"}],"name":"National Centre for Biological Sciences-TIFR, GKVK Campus 1 , Bangalore,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4778-1364","authenticated-orcid":true,"given":"Amruta","family":"Naik","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03gf8rp76","id-type":"ROR","asserted-by":"publisher"}],"name":"National Centre for Biological Sciences-TIFR, GKVK Campus 1 , Bangalore,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2281-078X","authenticated-orcid":true,"given":"Ujjaini","family":"Dasgupta","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02n9z0v62","id-type":"ROR","asserted-by":"publisher"}],"name":"Amity Institute of Integrative Sciences and Health, Amity University Haryana 2 , Gurgaon,","place":["India"]},{"name":"Trivedi School of Biosciences, Ashoka University 3 Department of Biology and Koita Centre for Digital Health-Ashoka, , Sonipat,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3578-6413","authenticated-orcid":true,"given":"Padinjat","family":"Raghu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03gf8rp76","id-type":"ROR","asserted-by":"publisher"}],"name":"National Centre for Biological Sciences-TIFR, GKVK Campus 1 , Bangalore,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"key":"2026090109512706600_bib1","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.neuron.2007.10.041","article-title":"Cell-nonautonomous function of ceramidase in photoreceptor homeostasis","volume":"57","author":"Acharya","year":"2008","journal-title":"Neuron"},{"key":"2026090109512706600_bib2","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1007\/s00018-004-4254-1","article-title":"Enzymes of sphingolipid metabolism in Drosophila melanogaster","volume":"62","author":"Acharya","year":"2005","journal-title":"Cell Mol. 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