In particular, we and others have shown that hyperphosphorylation of RyR2 at serine 2814 (S2814) by Ca2+/calmodulin-dependent protein kinase II (CaMKII) contributes to these RyR2 leaks and is implicated in both atrial fibrillation and heart failure; by contrast, genetic ablation of S2814 (mutating to an alanine, S2814A) rescues disease phenotypes in mice [3,4,5]. This evidence concerns the gene RYR2 and atrial fibrillation.