RYR2 and atrial fibrillation: In human AF models, enhanced spontaneous sarcoplasmic reticulum (SR) Ca2+ release has been attributed to ryanodine receptor (RyR2) dysregulation [14,15], Ca2+/calmodulin-dependent protein kinase-II (CaMKII) hyperactivity [16,17,18], or SPEG (striated muscle preferentially expressed protein kinase), a regulator of RyR2 phosphorylation and downregulation [19].