Altogether, our data indicate that in regard to the physiology of CPVT, pre-association of CaM to RyR2 is not altered; however, when intracellular Ca2+ increases during CICR, the decreased affinity for RyR2 reduces the inhibition of the channel and can promote Ca2+ release from the SR. Here, CALM1 is linked to catecholaminergic polymorphic ventricular tachycardia.