RYR1 and myopathy: Downregulated RyRs have been found in diseases such as sarcopenia (aged-related muscle weakness with a prevalence >20% in older adults) (4, –6), heart failure (aged-related cardiac weakness with a prevalence >5% in older adults) (7, , , –11), intensive care unit (ICU) muscle weakness (prevalence of 33% of ICU patients) (12), myopathies (13), and rare hereditary conditions such as RyR1-related diseases (14) and Ca2+ release deficiency syndrome (15).