First characterized in the late 1990s for its role in enhancing β-cell insulin sensitivity (Edwards et al., 1999; Scrocchi et al., 1996), this mechanism propelled the development of GLP-1 receptor agonists (GLP-1RAs), initially approved for diabetes (2005) and later for obesity (2014) (Jastreboff and Kushner, 2023). The gene discussed is GLP1R; the disease is obesity due to melanocortin 4 receptor deficiency.