MC4R and obesity due to melanocortin 4 receptor deficiency: MC4R is an important regulator of energy balance in humans, as loss-of-function MC4R mutations constitute the most common form of monogenic obesity (1); and more than 150 pathogenic MC4R variants have been identified in patients with severe, early-onset obesity accompanied by hyperphagia, increased linear growth, impaired glucose metabolism (2) and decreased heart rate and blood pressure compared with similarly obese controls (3).