We are beginning to determine the contribution of the central and peripheral ADGRL1 to glucose sensing, development of obesity and type 2 diabetes.1,2 Interestingly, clinical features in a cohort of humans with pathogenic ADGRL1 variants show that four out of nine individuals with the variants were overweight.5 Similarly, Dietzsch et al.1 also identified variants of the human LPHN1 that contribute to the obesity phenotype. This evidence concerns the gene ADGRL1 and obesity due to melanocortin 4 receptor deficiency.