Chloride intracellular channel protein family (CLIC)

The Chloride intracellular channel (CLIC) family represents a unique class of metamorphic proteins that exist in both soluble globular forms and membrane-integrated channel forms [UniProt]. In humans, the family comprises six members (CLIC1–CLIC6) that share a structural fold similar to glutathione S-transferase (GST) enzymes [PubMed: 29158348]. These proteins are involved in fundamental cellular processes such as ion homeostasis, cell cycle progression, and apoptosis [PubMed: 30305540]. CLIC1 and CLIC4 are particularly noted for their roles in disease; CLIC1 is essential for NLRP3 inflammasome activation and is upregulated in several cancers, while CLIC4 is involved in TGF-beta signaling and angiogenesis [PubMed: 28450786]. Therapeutic interest in CLICs stems from their potential as targets for anti-inflammatory and anti-neoplastic agents, with inhibitors like IAA-94 demonstrating the ability to block their channel activity [PubMed: 31434667]. However, the ubiquitous expression of these proteins and their complex structural transitions present significant challenges for drug development and safety [PubMed: 25100781].

Other names

Chloride intracellular channel proteinsCLIC proteinsNCC27-like proteins

Direct inhibition of chloride ion conductance and interference with the metamorphic transition from soluble to membrane-bound states.