In contrast to the latter compound that acts on SERCA2a and Na+/K+ ATPase (Micheletti et al, 2007), here we identify the first multi-targeted small compound with pronounced SR Ca2+ leak inhibitory and SR Ca2+ uptake stimulatory action in cardiomyocytes from mice and human, together with a prominent action in a human-associated mouse model of CPVT, thus opening avenues for the development of a novel class of RyR2 multi-target–directed ligands. This evidence concerns the gene RYR2 and catecholaminergic polymorphic ventricular tachycardia.