Conversely, dysregulation of RyR2 by a number of mechanisms can lead to inappropriate Ca2+ release during diastole (“RyR2 leak”), which is associated with several cardiac diseases including catecholaminergic polymorphic ventricular tachycardia, atrial fibrillation, and heart failure [2,3,4,5,6,7]. Here, RYR2 is linked to heart failure.