The interaction between KSR2 and AMPK has been suggested to underpin some of the abnormalities of energy homeostasis and metabolism seen in Ksr2−/− mice, which include obesity, high insulin levels, and impaired glucose tolerance (Brommage et al., 2008; Costanzo-Garvey et al., 2009; Revelli et al., 2011). This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.