The water-soluble so-called RyCal S107 inhibited both RyR2-mediated Ca2+ leak and stress-induced ventricular arrhythmias in RyR2R2474S/+ mice (Lehnart et al, 2008) and reduced heart failure progression in homozygous RyR2S2808D+/+ mice carrying a mutation that mimics PKA hyper-phosphorylation (Shan et al, 2010). Here, RYR2 is linked to heart failure.