Phospholamban is a major regulator of the kinetics of cardiac contractility, through its ability to regulate the function of the cardiac SR Ca(2+)-pump and thus the SR Ca2+ load. In vitro expression studies have provided significant information on the structure/function of the phospholamban/Ca(2+)-pump interaction. Furthermore, the generation of genetic animal models with altered phospholamban expression levels have permitted a through understanding of the physiological role of this regulatory phosphoprotein. Future studies aimed towards crystallization of phospholamban and the SR Ca(2+)-ATPase in their native SR environment may provide clues to their tertiary and quaternary structures and may further elucidate the mechanisms underlying the phospholamban regulatory effects in vivo.