cise-inducedsuddencardiacdeath.Thebestcharacterizedofthesehavebeen mutationsinthecardiacCa 2+ releasechannelknownastheryanodinereceptor type2(RyR2).RyR2mutationscause"leaky"channels,resultingindiastolic Ca 2+ leakfromthesarcoplasmicreticulum(SR)thatcantriggerfatalcardiac arrhythmiasduringstress.InthisissueoftheJCI,Songetal.showthatmuta- tionsintheSRCa 2+ -bindingproteincalsequestrin2(CASQ2)inmiceresult notonlyinreducedCASQ2expressionbutalsoinasurprising,compensa-