KSR2 mutations in humans (Pearce et al. 2013) recapitulate the obesity and severe insulin resistance observed in C57BL/6 ksr2−/− mice (Costanzo‐Garvey et al. 2009), revealing them as a disease‐relevant model system, allowing investigation into mechanisms through which KSR2‐dependent signaling may contribute to the onset and progression of obesity and diabetes in humans. This evidence concerns the gene KSR2 and obesity due to melanocortin 4 receptor deficiency.