Interestingly, all our previous reports on the characterization of various arrhythmogenic CaM mutants support the notion that the clinical presentation of LQTS or CPVT associated with CaM mutations may involve a combination of both altered intrinsic Ca2+-binding to CaM, as well as a defective interaction of CaM with RyR2 that leads to defective regulation of this channel [35,36,37,38]. This evidence concerns the gene CALM3 and catecholaminergic polymorphic ventricular tachycardia.