The present study markedly extends these earlier studies by showing that in patient-specific CMs, the CPVT RyR2-D3638A mutation causes a macromolecular complex remodeling including depletion of Calstabin2 under stress, indicating that such RyR2 post-translational modifications are a mechanism in human CMs, which we believe to be novel to explain stress-induced ventricular arrhythmias and pharmacological responses observed clinically including inappropriate response to standard β-adrenergic receptor blockade. This evidence concerns the gene RYR2 and Ventricular arrhythmia.