Additionally, SERCA2 activity and expression are diminished in vascular smooth muscle26,27 and heart28,29 in different animal models of obesity/diabetes, highlighting a potential pathological role for SERCA2 dysfunction and disturbed intracellular Ca2+ homeostasis in the development of metabolic abnormalities in insulin resistance and diabetes. This evidence concerns the gene ATP2A2 and obesity due to melanocortin 4 receptor deficiency.