The association of sulfonylurea receptors (SURs) with K(IR)6X subunits to form ATP-sensitive K+ channels presents perhaps the most unusual function known for members of the transport ATPase family. The integration of these two protein subunits extends well beyond conferring sensitivity to sulfonylureas. Recent studies indicate SUR-K(IR)6.x interactions are critical for all of the properties associated with native K-ATP channels including quality control over surface expression, channel kinetics, inhibition and stimulation by Mg-nucleotides and response both to channel blockers like sulfonylureas and to potassium channel openers. K-ATP channels are a unique example of the physiologic and medical importance of a transport ATPase and provide a paradigm for how other members of the family may interact with other ion channels. (C) 1999 Published by Elsevier Science B.V. All rights reserved.