Chloride is a critical component of all living cells. Voltage-gated chloride channels regulate cellular traffic of chloride ion. The chloride channels (CIC or CLC) performs several functions including the regulation of cell volume, membrane potential stabilization, signal transduction, and transepithelial transport. Mutations in CIC genes have been linked with several human diseases including myotonias (Thomsen's disease), cystic fibrosis, Bartters syndrome type III, Dent's disease, and X-linked recessive nephrolithiasis. In mammals, CLC proteins form a superfamily of at least 9 different genes (CLC1-7 also known as CLCN1-7 and CLK1-2 or CLCKa and CLCKb). Additional forms of these proteins are obtained by alternative splicing. All CLC proteins (~700-1000 aa) are predicted to contain 10 (possibly 12) transmembrane domains.Except CLC-1 and CLC-K1/K2 that are specific for kidney, most other CLC are widely distributed in various tissues.