Sumoylation is a widespread posttranslational modification thought to affect primarily nuclear proteins, especially transcription factors for which sumoylation usually results in repression of their transactivational function. Recent proteomics studies have greatly expanded the cadre of known SUMO substrates, and an increasing number of cytoplasmic proteins have been identified as SUMO targets. However, very few of these cytosolic proteins have been evaluated for the functional consequences of sumoylation. Rajan et al. now demonstrate that the activity of an integral cytoplasmic membrane channel-forming protein, K2P1, is completely abrogated by sumoylation at a single lysine residue on the cytoplasmic tail. This is the first report of a plasma membrane protein as a SUMO substrate and explains the long-standing inability to demonstrate functionality of K2P1. Apparently, K2P1 is stoichiometrically sumoylated under most cellular conditions, so it is constitutively inactive until desumoylated. These observations raise several intriguing questions, including: How and where does K2P1 become sumoylated? Why, unlike most known substrates, is K2P1 so efficiently sumoylated? and, What are the signals and SUMO proteases that trigger K2P1 desumoylation? But most importantly, the report by Rajan et al. expands the functional roles attributed to sumoylation into the new arena of membrane protein functional regulation and suggests that similar mechanisms may regulate the function of other pore proteins.