Over the years, several lines of evidence have outlined a critical role of the adenosine system in glucose homeostasis, inflammation, adipogenesis, insulin resistance and thermogenesis, thus suggesting an involvement of adenosine in the onset and progression of obesity (Pardo et al., 2017; D’Antongiovanni et al., 2020b). The gene discussed is INS; the disease is obesity due to melanocortin 4 receptor deficiency.