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In astrocytes, the MLC protein MLC1 partially sequesters GPRC5B, thereby reducing the GPRC5B\u2013LRRC8A interaction, providing a mechanistic link to VRAC dysfunction in megalencephalic leukoencephalopathy. These results reveal a receptor-kinase-channel pathway that gates VRAC through Y362-dependent modulation of LRRC8A, establishing a molecular framework for VRAC regulation and its disruption in disease.<\/jats:p>","DOI":"10.1073\/pnas.2606899123","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T17:37:33Z","timestamp":1792085853000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["A GPRC5B\u2013Fyn signaling axis regulates VRAC activity by targeting LRRC8A"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9933-2918","authenticated-orcid":false,"given":"Yulia","family":"Kostritskaia","sequence":"first","affiliation":[{"name":"Institute for Molecular Medicine, MSH Medical School Hamburg","place":["Hamburg, 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