Whereas, “pure” LQTS and CPVT phenotypes suggest abnormal modulation of ICaL and RyR2, respectively, we hypothesize that coexistence of QT prolongation and SR instability (mixed phenotypes) might be accounted for by impaired ICaL CDI, possibly with the complement of (very common) conditions weakening homeostatic control of intracellular Ca2+. This evidence concerns the gene RYR2 and familial long QT syndrome.