Given that the pancreatic CRL4COP1–ETV5 axis is hyperactive not only in Csn2WT/K70E mice (Fig. 3), but also in HFD-fed mice (Fig. 7a), we examined whether CRL inhibition could rescue disease progression in this obesity/diabetes model. This evidence concerns the gene ETV5 and obesity due to melanocortin 4 receptor deficiency.