CACNA1C and familial long QT syndrome: Boczek et al. revealed that CACNA1C-P857A induces LQTS by causing a gain-of-function of ICa, L and an increase of CaV1.2 membrane trafficking and speculates the modulation might be because the mutation locates at the conserved proline, glutamic acid, serine, and threonine rich (PEST) domain of CaV1.2 II-III loop, which acts to proteolytic signaling through the cellular “quality control” system (PEST1 is S446/459, and PEST3 is S840/861) (23).