Post-translational modification of RyR2 by PKA and/or CaMKII phosphorylation may increase the RyR2 Ca2+ sensitivity and has been attributed as a possible cause of the hyperactive RyR2 observed in heart failure, although the physiological consequences and precise locations of phosphorylation are still the matter of ongoing investigation (for a recent review see [130]). The gene discussed is RYR2; the disease is heart failure.