CLIC6 is a chloride intracellular channel protein that exists in both soluble and membrane-bound forms. In its soluble state, CLIC6 catalyzes glutaredoxin-like thiol-disulfide exchange reactions 1. Upon membrane insertion, CLIC6 forms voltage-dependent, chloride-selective ion channels that open during membrane depolarization at positive voltages and close at negative voltages 1. The channel is regulated by pH and redox potential through histidine-648 and cysteine-487 residues 1. CLIC6 is abundantly expressed in lung and brain tissues 1 and interacts with dopamine D2, D3, and D4 receptors through its C-terminal cytoplasmic tail, potentially functioning within multi-protein scaffolding complexes 2. In retinal pigment epithelium, CLIC6 plays a critical role in maintaining proper apical microvilli morphology and organization; CLIC6 deficiency causes broadened, stunted microvilli and increased phagosome density 3. Clinically, CLIC6 serves as a methylation-driven prognostic biomarker in breast cancer, where decreased expression correlates with improved survival, enhanced CD8+ T cell infiltration, and a more immunogenic tumor microenvironment 4. CLIC6 is also identified as a lactate-related biomarker in nasopharyngeal carcinoma associated with immune cell activation pathways 5 and appears dysregulated in suicide-associated brain transcriptome alterations 6.