Here, we demonstrate first that intestinal contractility is reliant on Kir6.1 and SUR2 expression in smooth muscle and, secondly, that pathogenic mutations within ABCC9 and KCNJ8, both of which underlie Cantú syndrome (CS), result in impaired contractility and motility in both small intestine and colon. The gene discussed is ABCC9; the disease is Cowden syndrome 1.