There are also some clinical data in support of a contribution of the “Ca2+ clock” through patients with catecholaminergic polymorphic ventricular tachycardia (CPVT), who have an impaired Ca2+ clock due to mutations in the RYR2 gene (CPVT1) or the CASQ2 gene (CPVT2), encoding the cardiac ryanodine receptor isoform 2 (RyR2, responsible for Ca2+ release from the SR) and the cardiac calsequestrin isoform 2 protein (calsequestrin-2, responsible for calcium buffering in the SR), respectively [15]. Here, CLOCK is linked to catecholaminergic polymorphic ventricular tachycardia.