Chloride (Cl^-) channels are membrane, anion-selective protein pores, which diffusively transport negative ions across their electrochemical gradient. Cl^- channels are subdivided into six unique families, and their regulation mechanisms range from voltage-dependency, through G-protein activation, to mechanosensitivity; they may reside in either the plasma membrane or the membrane of intracellular compartments or both¹. They are detected in the kidney, placenta, intestines, brain and the inner-ear^1-4. 

The vertebrate Cl^- intracellular channel (CLIC) family is composed of 6 highly conserved members (CLIC1-6); each exists as a ~250 residue protein which can assume both a soluble fold and a membrane-integral form. The latter consists of a single trans-membrane domain and is subsequently oligomerized to construct a functioning channel^1,5. Interestingly, channels composed of CLIC4 and CLIC5 have been confirmed to be equally permeable to K⁺ and Cl^-5.

CLIC5, to which there are two isoforms  - CLIC5A and CLIC5B - encoded by the same gene⁵, has first been isolated from human placenta⁶, and was shown, together with CLIC4 (with which it shares 76% homology), to be enriched in the apical microvilli-containing part of the trophoblast epithelium, where, unlike CLIC4, it interacts with the actin cytoskeleton⁴. CLIC5 shares about 40% homology with CLIC1-4 and is distributed to a high degree in myocytes, cardiomyocytes and stereocillia of the inner-ear^2,4. Mice mutated in the Clic5 gene lack coordination and gradually become deaf², show resistance to obesity, experience gastric ulcers and the resultant hemorrhage, and have higher incidence of entering torpor⁷.