RYR1 and Malignant hyperthermia: The hierarchy of these “hot spots” in the control of the channel’s stability is also demonstrated by the fact that equivalent mutations in RYR1, the gene encoding for the skeletal isoform of the RyR (RyR1), give rise to Malignant Hyperthermia and Central Core Disease, two devastating diseases of skeletal muscle whose primary pathogenic mechanism is also excessive Ca2+ leak from the SR [23].