Given that both PKG and PKA have been implicated as targets in disease conditions such as dilated cardiomyopathy (35, –, 37), heart failure with preserved ejection fractions (38, 39), and ischemia reperfusion injury (40, 41), characterization of RIα phosphorylation within endogenous tissues may further bolster the significance of this mechanism within the context of clinically relevant cardiovascular diseases. This evidence concerns the gene PRKG1 and dilated cardiomyopathy.