Calstablin2 stabilises the ryanodine receptor (RyR2), preventing aberrant 
activation of the channels during the resting phase of the cardiac muscle. Loss 
of this stabilisation may be associated with cardiac arrhythmias, the sudden 
death occasionally observed in people with structurally normal hearts, as well 
as the atrial fibrillation in heart failure. Calstabin2-deficient mice have 
structurally normal hearts but exhibit exercise-induced cardiac ventricular 
arrhythmias that cause sudden death. In arrhythmias, the calstabin2 stabiliser 
JTV519 did not prevent arrhythmias in calstabin2-/- mice, but reduced the 
arrhythmias in calstabin2+/- mice, illustrating the antiarrhythmic potential of 
stabilising calstablin2. Familial polymorphic ventricular tachycardia in humans 
has been linked to missense mutants in the hRyR2 gene. In HEK293 cells, these 
RyR2 mutants showed less binding of 35S-calstabin2 than the wild type, 
indicating a reduced binding affinity. In human atrial fibrillation and heart 
failure, where there is excessive disassociation of calstabin2 from the RyR2 
receptor in vitro, JTV519 is able to reverse this. In conclusion, calstabin2 is 
an important new target in sudden cardiac death associated with structurally 
normal hearts, and in the treatment of atrial fibrillation and heart failure.