Dilated cardiomyopathy is a disease of the heart muscle resulting from a diverse 
array of conditions that damages the heart and impairs myocardial function. 
Heart failure occurs when the heart is unable to pump blood at a rate which can 
accommodate the heart muscle's metabolic requirements. Several signaling 
pathways have been shown to be involved in the induction of cardiac disease and 
heart failure. Many of these pathways are linked to cardiac sarcoplasmic 
reticulum (SR) Ca cycling directly or indirectly. A large body of evidence 
points to the central role of abnormal Ca handling by SR proteins, Ca-ATPase 
pump (SERCA2a) and phospholamban (PLN), in pathophysiological heart conditions, 
compromising the contractile state of the cardiomyocytes. This review summarizes 
studies which highlight the key role of these two SR proteins in the regulation 
of cardiac function, the significance of SERCA2a-PLN interactions using 
transgenic approaches, and the recent discoveries of human PLN mutations leading 
to disease states. Finally, we will discuss extrapolation of experimental 
paradigms generated in animal models to the human condition.