The physiological regulation of RyR2 Ca2+ release is tightly controlled, and a defective inhibition of the open probability of this channel might be a common factor of both LQTS and CPVT arrhythmias caused by CaM mutations, resulting in abnormal RyR2 Ca2+ release. Here, CALM2 is linked to catecholaminergic polymorphic ventricular tachycardia.