In the present study, we explored the mechanistic role of atrial RyR2 oxidation in the pathophysiology of AF in two murine models of RyR2-mediated intracellular Ca2+ leak: mice harboring an RyR2 mutation linked to human CPVT (RyR2-R2474S+/–) and mice expressing a phosphomimetic aspartic acid residue at position 2808 (RyR2-S2808D+/+) leading to constitutively leaky channels. The gene discussed is RYR2; the disease is atrial fibrillation.