Phospholamban (PLN) is a small phosphoprotein closely associated with the 
cardiac sarcoplasmic reticulum (SR). Dephosphorylated PLN tonically inhibits the 
SR Ca-ATPase (SERCA2a), while phosphorylation at Ser16 by PKA and Thr17 by 
Ca(2+) /calmodulin-dependent protein kinase (CaMKII) relieves the inhibition, 
and this increases SR Ca(2+) uptake. For this reason, PLN is one of the major 
determinants of cardiac contractility and relaxation. In this review, we 
attempted to highlight the functional significance of PLN in vertebrate cardiac 
physiology. We will refer to the huge literature on mammals in order to describe 
the molecular characteristics of this protein, its interaction with SERCA2a and 
its role in the regulation of the mechanic and the electric performance of the 
heart under basal conditions, in the presence of chemical and physical stresses, 
such as β-adrenergic stimulation, response to stretch, force-frequency 
relationship and intracellular acidosis. Our aim is to provide the basis to 
discuss the role of PLN also on the cardiac function of nonmammalian 
vertebrates, because so far this aspect has been almost neglected. Accordingly, 
when possible, the literature on PLN will be analysed taking into account the 
nonuniform cardiac structural and functional characteristics encountered in 
ectothermic vertebrates, such as the peculiar and variable organization of the 
SR, the large spectrum of response to stresses and the disaptive absence of 
crucial proteins (i.e. haemoglobinless and myoglobinless species).