Chloride intracellular channel protein 1

CLIC1 (chloride intracellular channel protein 1) is a 241-amino-acid protein with dual functionality as a soluble thiol disulfide oxidoreductase and a membrane-insertable ion channel (UniProt: O00299). In its soluble state, CLIC1 catalyzes glutaredoxin-like reactions using reduced glutathione as electron donor, reducing selenite and dehydroascorbate and functioning as an antioxidant during oxidative stress. Under oxidizing conditions, it can insert into membranes to form voltage-dependent multi-ion conductive channels and is implicated in cell cycle regulation (UniProt: O00299).

CLIC1 has no primary disease associations listed in UniProt; however, it is curated as disease-relevant in Alzheimer's Disease. In post-mortem AD brain tissue, CLIC1 is significantly upregulated compared to age-matched controls across subcellular fractions (mean log2 fold-change: 0.97; Chaparral AD proteomics). This upregulation was detected via TMT-labeled proteomics across four subcellular fractions (P2, P3, S2, S3), suggesting CLIC1 may be involved in oxidative stress responses or membrane dysfunction pathways implicated in AD pathology.