This is a significant role given the deleterious effects of changes in resting RyR activity or ‘leak’ in causing myopathies such as central core disease and malignant hyperthermia in skeletal muscle (Dainese et al., 2009; Paolini et al., 2007) and in precipitating cardiac arrhythmia (Jiang et al., 2004; Terentyev et al., 2006). Here, RYR2 is linked to Malignant hyperthermia.