CLC-2 is a member of the voltage-dependent Cl^- channel (CLC) family that includes nine known members in mammals. CLC channels can be classified as plasma membrane channels and intracellular organelle channels. The first group includes the CLC-1, CLC-2 CLC-Ka and CLCKb channels. The second group comprises the CLC-3, CLC-4, CLC-5, CLC-6 and CLC-7.

CLC channels that function in the plasma membrane are involved in the stabilization of membrane potential and in transepithelial transport. The presumed function of the intracellular CLC channels is support of the acidification of the intraorganellar compartment. In this regard, recent reports indicate that ClC-4 and ClC-5 (and by inference ClC-3) can function as Cl^-/H⁺ antiporters.^{1, 2}

The functional unit of the CLC channels is a dimer with each subunit forming a proper pore. Although the crystal structure of bacterial CLC channels was resolved, the topology of the CLC channels is complex and has not been fully elucidated. It is generally accepted that both the N- and C- terminus domains are intracellular while the number and configuration of the transmembrane domains vary greatly between different models. ^1,2

CLC-2 is widely distributed with prominent expression in brain, kidney, lung and the gastrointestinal system.  Mutations in the CLC-2 channel gene detected in humans are associated with idiopathic generalized epilepsies while disruption of the ClC-2 gene in mice is associated with testicular and retinal degeneration. ^3,4