Ventricular arrhythmias can cause sudden cardiac death (SCD) in patients with 
normal hearts and in those with underlying disease such as heart failure. In 
animals with heart failure and in patients with inherited forms of 
exercise-induced SCD, depletion of the channel-stabilizing protein calstabin2 
(FKBP12.6) from the ryanodine receptor-calcium release channel (RyR2) complex 
causes an intracellular Ca2+ leak that can trigger fatal cardiac arrhythmias. A 
derivative of 1,4-benzothiazepine (JTV519) increased the affinity of calstabin2 
for RyR2, which stabilized the closed state of RyR2 and prevented the Ca2+ leak 
that triggers arrhythmias. Thus, enhancing the binding of calstabin2 to RyR2 may 
be a therapeutic strategy for common ventricular arrhythmias.