In agreement with the clinical observations, our results indicated that the RyR2-D3638A mutation in CPVT hiPSC-CMs leads to an abnormal Ca2+ release under stress conditions by decreasing the Ca2+ transient amplitude and increasing the occurrence of both, the systolic and diastolic aberrant Ca2+ events. Here, RYR2 is linked to catecholaminergic polymorphic ventricular tachycardia.