Alterations in the functions of RyR2 or SERCA2a canlead to impaired heart function and various pathological conditionsincluding heart failure (HF) and cardiac arrhythmias.−, , ,  In HF, for instance, RyR2 channels are hyperphosphorylated by proteinkinase A (PKA) and Ca2+-calmodulin-dependent kinase II(CaMKII), impairing binding of the stabilizing subunit, calstabin2,and rendering the channels leaky for SER Ca2+. Here, RYR2 is linked to chronic obstructive pulmonary disease.