A second-generation MC4R agonist reduced weight in rare patients with obesity due to genetic disruption of the melanocortin pathway (Clément et al., 2018, Collet et al., 2017, Kühnen et al., 2016) without affecting BP (Chen et al., 2015, Kievit et al., 2013); however, off-target effects on the melanocortin-1 receptor (skin pigmentation) may limit its wider use. The gene discussed is MC4R; the disease is obesity disorder.