RYR2 and heart failure: Our studies of HRC using the partial KD systems appears to be beneficial and provided several novel findings as follows: 1) Both RyR2 and SERCA activities were enhanced by KD of HRC (Figures 1, 4 and Figure S3), 2) The increased RyR2 activity could directly cause the increased resting and peak Ca2+ concentrations (Figures 2, 3 and S2), 3)) Heart failure (HF) induced by TAC was further exacerbated by HRC-KD (Figure 6) and 4) The exacerbated HF by HRC-KD is due at lease in part to the cytosolic Ca2+-leak and enhanced mitochondrial death pathways (Figures 7 and 8).