RYR2 and heart failure: Suetomi et al. studies have shown that when RyR2 deficiency or expression decreases, Ca2+ spontaneously leaks from the sarcoplasmic reticulum (Suetomi et al., 2011), which influences the calcium homeostasis of cardiomyocytes, reduces the production of ATP from mitochondria, and leads to heart failure due to cardiac systolic dysfunction.