INTRODUCTION: Calcium-calmodulin-dependent protein kinase II (CaMKII) has 
emerged as a central mediator of cardiac stress responses which may serve 
several critical roles in the regulation of cardiac rhythm, cardiac 
contractility and growth. Sustained and excessive activation of CaMKII during 
cardiac disease has, however, been linked to arrhythmias, and maladaptive 
cardiac remodeling, eventually leading to heart failure (HF) and sudden cardiac 
death.
AREAS COVERED: In the current review, the authors describe the unique structural 
and biochemical properties of CaMKII and focus on its physiological effects in 
cardiomyocytes. Furthermore, they provide evidence for a role of CaMKII in 
cardiac pathologies, including arrhythmogenesis, myocardial ischemia and HF 
development. The authors conclude by discussing the potential for CaMKII as a 
target for inhibition in heart disease.
EXPERT OPINION: CaMKII provides a promising nodal point for intervention that 
may allow simultaneous prevention of HF progression and development of 
arrhythmias. For future studies and drug development there is a strong rationale 
for the development of more specific CaMKII inhibitors. In addition, an improved 
understanding of the differential roles of CaMKII subtypes is required.