The COP1 protein, first identified in Arabidopsis based on the constitutive photomorphogenesis (COP) phenotype of its mutants, is a candidate CRL4 substrate receptor that promotes murine insulin secretion by ubiquitylating the ETV family of transcription factors8,9, among which, ETV5 is strongly associated with obesity and T2D according to genome-wide association studies (GWAS)10–12. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.