Sterol hindrance of Orai activation

Orai channels at the plasmamembranemediate store-operatedCa²⁺ entry in response to Ca²⁺ depletion of the endoplasmic reticulum. Orai channels are gated by stromalinteractingmolecule proteins, which act as Ca²⁺ sensors, and the association of these proteins is enhanced in cholesterol-rich lipid rafts. In research published in Science Signaling, Derler et al. report that cholesterol inhibits Orai function through direct association with the channel amino terminus.