The chloride intracellular channel 1 (CLIC1) is essential for microglial morphodynamics and neuroinflammation.

ABSTRACT: Microglial functions rely on their morphodynamic versatility and inflammatory response, yet the molecular determinants, particularly ion channels and receptors, remain poorly understood. Here, we identify chloride intracellular channel 1 (CLIC1), a protein known to exist in both soluble and membrane-associated forms, as highly enriched in human and murine microglia, with minimal expression in other brain cells. Acute blockade or genetic deletion of CLIC1 markedly attenuates microglial surveillance by reducing ramification and motility, without affecting chemotaxis. This phenotype is recapitulated in xenografted human microglia and human brain tissue. Mechanistically, CLIC1 effects involve interactions with actin-binding ezrin, radixin, and moesin (ERM) proteins, suggesting a role in linkin

SUBMITTER: Rifat A 

PROVIDER: S-EPMC12542960 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature