RYR2 and catecholaminergic polymorphic ventricular tachycardia: We have previously reported that either a single point mutation, hyperphosphorylation, or oxidative stress commonly causes domain unzipping between the N-terminal and central domains, which allosterically displaces calmodulin (CaM) from RyR2, thus leading to Ca2+ leakage in a CPVT-associated RyR2R2474S/+ knock-in mouse model9–12 and also in a canine model of tachycardia-induced heart failure13–17.