ATP-sensitive K⁺ channels (K_ATP channels) play important roles in many cellular functions by coupling cell metabolism to electrical activity. By cloning members of the novel inwardly rectifying K⁺ channel subfamily Kir6.0 (Kir6.1 and Kir6.2) and the receptors for sulfonylureas (SUR1 and SUR2), researchers have clarified the molecular structure of K_ATP channels. K_ATP channels comprise two subunits: a Kir6.0 subfamily subunit, which is a member of the inwardly rectifying K⁺ channel family; and a SUR subunit, which is a member of the ATP-binding cassette (ABC) protein superfamily. K_ATP channels are the first example of a heteromultimeric complex assembled with a K⁺ channel and a receptor that are structurally unrelated to each other. Since 1995, molecular biological and molecular genetic studies of K_ATP channels have provided insights into the structure-function relationships, molecular regulation, and pathophysiological roles of K_ATP channels.