The role of RyR2 in the pathophysiology of HF and CPVT will be discussed in the context of its role in ECC, and the mechanisms underlying dysfunction and how these might be changed by phosphorylation, RyR2 interaction with regulatory proteins, Ca2+ homeostasis or abnormal intra RyR2 domain interactions. This evidence concerns the gene RYR2 and catecholaminergic polymorphic ventricular tachycardia.