All mammalian ClC channels and transporters exhibit cytoplasmic carboxy-termini containing two conserved CBS (cystathionine-beta-synthase) domains connected by a variable linker. We examined the role of the C-terminus of ClC-2, a chloride channel involved in epithelial salt resorption and regulation of [Cl-] in neurons. While deletion of one of the two CBS domains or parts of the CBS-CBS linker completely abolished anion currents, ClC-2 channels were functional after complete removal of the C-terminal domain. None of the tested channel truncations affected intracellular trafficking as assessed by immunohistochemistry. ClC channels display two kinetically distinct gating processes, a fast gate acting on individual protopores, and a slow gate conferring cooperative opening and closing transitions. Carboxy-terminal truncations significantly reduce the contribution of the slow gate to the open probability and enhance fast and slow activation and deactivation rates of ClC-2 channels. Heterodimeric channels with one WT and one partially truncated subunit exhibit novel properties indicating a functional interaction of the two C-termini. Our results suggest that the intra-molecular CBS interactions are not needed for the channel function and revealed a significant role of the CBS-CBS linker. The function of the ClC-2 C-terminus greatly differs from the one of ClC-1, where individual C-termini only affect the corresponding protopore, and where partial, but not complete deletions were functionally tolerated.