TRPV4 channel activity is modulated by direct interaction of the ankyrin domain to PI(4,5)P2

Mutations in the ankyrin repeat domain (ARD) of TRPV4 are responsible for several channelopathies but little is known about the physiological function of this domain. Here the authors show that phosphoinositide binding to TRPV4 ARD leads to suppression of the channel activity, and obtain the crystal structure of the domain in complex with inositol-1,4,5-trisphosphate.