Calcium and the failing heart: phospholamban, good guy or bad guy?

In cardiac cells, phospholamban is a potent inhibitor of sarcoplasmic reticulum calcium (Ca(2+)) transport. Overexpression of mutant forms of phospholamban may result in beneficial or detrimental effects on intracellular Ca(2+) handling and cardiac systolic and diastolic function. Mutations in phospholamban have also been linked to human cardiomyopathies, providing important insights into the underlying disease mechanisms and the key role of phospholamban in myocardial excitation-contraction coupling. This Perspective discusses new advances in our understanding of the role of phospholamban in intracellular Ca(2+) handling and the development of human and murine cardiomyopathies.