RYR2 and catecholaminergic polymorphic ventricular tachycardia: The question is relevant because, scanning the phenotype of several RyR2 channels harboring CPVT mutations, Chen and co-workers [32] found that at least one of them, RyR2-A4860G, exhibited a pronounced loss-of-function characterized by a markedly depressed response to luminal Ca2+ and extremely low open probability in the presence of full agonists such as cytosolic Ca2+ and caffeine.