The phenotype of C57BL/6 ksr2−/− mice, including obesity and obesity‐related dysregulation of glucose homeostasis, recapitulates that of humans with KSR2 mutations, demonstrating the applicability of the C57BL/6 ksr2−/− mouse model to the study of the pathogenesis of human disease. This evidence concerns the gene KSR2 and obesity due to melanocortin 4 receptor deficiency.