Two decades with dimorphic Chloride Intracellular Channels (CLICs)

Plasma membrane channels have been extensively studied, and their physiological roles are well established. In contrast, relatively little information is available about intracellular ion channels. Chloride Intracellular Channel (CLICs) proteins are a novel class of putative intracellular ion channels. They are widely expressed in different intracellular compartments, and possess distinct properties such as the presence of a single transmembrane domain, and a dimorphic existence as either a soluble or membranous form. How these soluble proteins unfold, target to, and auto-insert into the intracellular membranes to form functional integral ion channels is a complex biological question. Recent information from studies of their crystal structures, biophysical characterization and functional roles has provoked interest in these unusual channels.