CLIC1 (chloride intracellular channel 1) functions as a multifaceted protein with dual roles in redox regulation and ion transport. In its soluble state, CLIC1 catalyzes glutaredoxin-like thiol-disulfide exchange reactions and acts as an antioxidant during oxidative stress 12. The protein can insert into membranes under oxidizing conditions to form voltage-dependent chloride channels, a process regulated by the cellular redox state 3. CLIC1 regulates cell cycle progression, particularly facilitating G1/S phase transition 3. CLIC1 has emerged as a critical oncogenic driver across multiple cancer types. In pancreatic cancer, elevated CLIC1 expression—induced by matrix stiffness through Wnt/β-catenin/TCF4 signaling—promotes the Warburg effect by stabilizing HIF1α through ROS suppression of hydroxylation, driving tumor growth 4. In glioblastoma, CLIC1 promotes cancer stem cell self-renewal and regulates glioma stem-like cells, contributing to therapy resistance and recurrence 3. In gallbladder and gastric cancers, CLIC1 silencing inhibits proliferation and invasion while promoting apoptosis 56. Mechanistically in gastric cancer, CLIC1 directly interacts with PKM2, stabilizing its dimeric form to enhance glycolytic metabolism 6. Beyond cancer, CLIC1 is upregulated in inflammatory and metabolic diseases. It serves as a disease-specific gene signature in acute pancreatitis 7 and functions as a diagnostic biomarker for Kawasaki disease, where it is elevated in monocytes involved in bile acid and fatty acid metabolism 8. In kidney disease, CLIC1 is upregulated in mesangial cells of IgA nephropathy 9.