In addition, familial and early-onset AF have been linked with rare variants of two CACNA genes with overlapping effects on the Cav1.2 (encoded by CACNA1C) [20] or junctophilin 2 (JPH2) resulting in defective RyR2-mediated sarcoplasmatic reticulum Ca(2+) release [21]. Here, RYR2 is linked to atrial fibrillation.