Protective roles against obesity and related metabolic derangements appear to be specific to CRTC1 among the CRTC family members, as evidenced by the obesity phenotypes observed in mice lacking an individual CRTC family member4; obese Crtc1−/−, near normal Crtc2−/−, and lean Crtc3−/− under chow diet. The gene discussed is CALR; the disease is obesity due to melanocortin 4 receptor deficiency.