Abstract:The major cause of human and experimental heart failure is related to the deregulated sarcoplasmic reticulum (SR) calcium cycling, controlled by several protein complexes. Those complexes, including protein kinase, protein phosphatase and some interacting proteins or subunits, work together to maintain normal cytosolic calcium homeostasis. Among them, SR calcium transport is regulated by SR calcium ATPase and the phosphorylated protein: phospholamban (PLN). Recently, some other proteins,such as: protein phosphatase 1 inhibitor 1, heat shock protein 20 (HSP20) and HS-associated protein X-1 (HAX-1) have been reported to play an important role in SR calcium handing as well as cardiac function. This review will focus on the recent findings in these PLN interacting complex and their contribution in cardiac pump function as well as the potential clinical application.