Sarcoplasmic reticulum (SR) Ca2+ ATPase (SERCA2a) transports Ca2+ into the SR, 
decreasing the cytosolic Ca2+ during relaxation and increasing the SR Ca2+ 
available for contraction. SERCA2a activity is regulated by phosphorylation of 
another SR protein: Phospholamban (PLN). Dephosphorylated PLN inhibits SERCA2a. 
Phosphorylation of PLN by either cAMP or cGMP-dependent protein kinase at Ser16 
or the Ca2+-calmodulin-dependent protein kinase (CaMKII), at Thr17, relieves 
this inhibition, increasing SR Ca2+ uptake and SR Ca2+ load. Thus, PLN is a 
major player in the regulation of myocardial relaxation and contractility. This 
review will examine the main aspects of the role of CaMKII and Thr17 site of 
PLN, on different pathophysiological conditions: acidosis, ischemia/reperfusion 
(I/R) and heart failure (HF). Whereas CaMKII-activation and PLN phosphorylation 
contribute to the functional recovery during acidosis and stunning, CaMKII 
results detrimental in the irreversible I/R injury, producing apoptosis and 
necrosis. Phosphorylation of Thr17 residue of PLN and CaMKII activity vary in 
the different models of HF. The possible role of these changes in the depressed 
cardiac function of HF will be discussed.