RYR2 and cardiac rhythm disease: This SR Ca2+ leak via calstabin2-depleted highly phosphorylated RyR2 channels had two major adverse consequences: (a) depletion of the SR Ca2+ store, directly impairing contractility (46); and (b) aberrant release of Ca2+ during diastole, causing delayed after-depolarizations (DADs) that trigger fatal cardiac arrhythmias (3).