When dysfunctional interactions between CaM and RyR2 occur, e.g., due to mutations associated to a CPVT phenotype (CPVT-CaM), SR Ca2+ content, along with its feedback mechanism, are dysregulated, leading to premature and spontaneous Ca2+ releases from the SR and arrhythmogenic propensity (48) (Figure 2B). This evidence concerns the gene CALM1 and catecholaminergic polymorphic ventricular tachycardia.