biostudies-literatureRahman MMCanadian Federation of University WomenCanadian Institutes of Health Research110646https://www.ebi.ac.uk/biostudies/studies/S-EPMC12494564biostudies-literatureUnknown301(10)Ezrin, radixin, and moesin (ERM) proteins regulate assembly of actin-based structures, link membrane-spanning proteins to cortical actin, and are part of cell signaling hubs. The chloride intracellular channel (CLIC) 5A protein is very abundant in radixin-dependent inner ear hair cell stereocilia and in ezrin-dependent kidney glomerular podocyte foot processes and is essential for the structural integrity of these actin-based cellular projections. The functional relationship between ERM proteins and CLIC5A is incompletely understood and whether CLIC5A functions as a chloride channel is controversial. We determined whether CLIC5A is membrane-spanning protein and sought direct CLIC5A binding partners. While CLIC5A localized predominantly to the dorsal plasma membrane domain, we found CLIC5A The Journal of biological chemistryCLIC5A binds to and stabilizes the open and active conformation of ezrin.PMC12494564169172Rahman MMFeisal MRTavasoli MBallermann BJMak KYLLi LWang ZKim JSHwang PMfalseCLIC5A binds to and stabilizes the open and active conformation of ezrin.Ezrin, radixin, and moesin (ERM) proteins regulate assembly of actin-based structures, link membrane-spanning proteins to cortical actin, and are part of cell signaling hubs. The chloride intracellular channel (CLIC) 5A protein is very abundant in radixin-dependent inner ear hair cell stereocilia and in ezrin-dependent kidney glomerular podocyte foot processes and is essential for the structural integrity of these actin-based cellular projections. The functional relationship between ERM proteins and CLIC5A is incompletely understood and whether CLIC5A functions as a chloride channel is controversial. We determined whether CLIC5A is membrane-spanning protein and sought direct CLIC5A binding partners. While CLIC5A localized predominantly to the dorsal plasma membrane domain, we found CLIC5A 2025-01-01T00:00:00Z2025 Aug2026-06-04T04:23:29.981Z2026-05-04T03:14:26.299ZS-EPMC124945644088538510.1016/j.jbc.2025.110646