Downregulation of RyRs activity has been found in diseases involving loss-of-function mutations (RyR1-related diseases and RyR2 calcium release deficiency syndrome) and reduced expression of RyRs (myopathies, sarcopenia, heart failure, cardiomyopathies, ICU muscle weakness, and others) (13, –15). The gene discussed is RYR2; the disease is heart failure.