Dysregulation of skeletal (RyR1) and cardiac (RyR2) isoforms, via mutations or excess posttranslational modification, has been linked to severe muscle pathologies, including malignant hyperthermia (MH), central core disease, muscular dystrophy (MD), sarcopenia, catecholaminergic polymorphic ventricular tachycardia, heart failure, and more recently RyR2 has been recognized as a potentially significant contributor to diabetes and Alzheimer’s disease1–9. This evidence concerns the gene RYR2 and Central core disease.