K_VLQT1 (KCNQ1) is a very small conductance K⁺ channel distributed widely in epithelial and non-epithelial tissues. Its specific biophysical and pharmacological properties are determined by the regulatory subunits I_sK (KCNE1) and MiRP2 (KCNE3). In epithelial cells of the inner ear, pancreas, and airways it interacts with I_sK to conduct a voltage-gated and slowly activating K⁺ current. In the colon it coassembles with KCNE3 to conduct an instantaneous and constitutively active K⁺ current. In Cl^– secretory epithelia, such as the colon and pancreas, this K⁺ channel provides the driving force for Cl^– exit and is located in the basolateral membrane. In the inner ear it enables luminal secretion of K⁺ into the endolymphatic space. The functional relevance of K_VLQT1 to epithelial function is revealed by blocking it pharmacologically or by studying animals with a genetic defect for it, which result in the breakdown of colonic Cl^– secretion and endolymph production, respectively. K_VLQT1 K⁺ channels are activated via cAMP or Ca²⁺ and inhibited by the chromanol 293B. Interaction with as yet unknown regulatory subunits may determine the properties of K_VLQT1 in the rectal gland and other epithelial tissues in which K_VLQT1 is not inhibited by chromanols.