Malignant ventricular arrhythmias (VA) are a major cause of mortality and morbidity worldwide. Causative mechanisms are multiple and complex. VA can be generated by abnormal or instable repolarization of the action potential (AP) in myocytes. Perverted repolarization results mainly from congenital channelopathies, acquired diseases, including hypertrophy and heart failure (HF), or therapeutic intervention. Inherited arrhythmias are due to mutations, mostly in transmembrane ionic channels (Na, K, Ca) [1,2]. However, because Ca regulates several ionic currents involved in AP repolarization , it was not counterintuitive to find that mutations in proteins regulating intracellular Ca homeostasis can also generate VA and sudden cardiac death (SCD). For example, mutations in the cardiac Ca release channel (ryanodine receptor; RyR2) of the sarcoplasmic reticulum (SR) are involved in type 2 arrhythmogenic right ventricular cardiomyopathy and catecholaminergic polymorphic ventricular tachycardia (CPVT) characterized by effort-induced VA in structurally normal hearts [2,4,5]. CPVT are also caused by mutations in calsequestrin, a protein binding Ca and associated to the RyR2 in the lumenal side of the SR [2,4].