An example of KATP channel overactivity leading to smooth muscle dysfunction is in the rare human disease, Cantú syndrome (CS).5 CS manifests as a result of gain-of-function (GoF) mutations in the genes encoding the “vascular smooth muscle” KATP channel, ABCC9 (SUR2), and less commonly in KCNJ8 (Kir6.1). Here, KCNJ8 is linked to Cowden syndrome 1.