Yamamoto et al. reported that the NH2-terminal (N: 0–600) and the central domains (C: 2000–2500) of RyR2 interact as a domain pair and either of these domains can have CPVT-linked RyR2 mutations, which modify the channels to be hyper-active and hyper-sensitive [15]. The gene discussed is RYR2; the disease is catecholaminergic polymorphic ventricular tachycardia.