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). This evidence concerns the gene RYR1 and sarcopenia.