A major breakthrough in the understanding of the pathophysiology of BSCL2 came with the generation of global knockout (KO) mice for Bscl2. Bscl2−/− mice display severe lipodystrophy, with at least a 90% decrease in WAT mass and the development of insulin resistance and hepatic steatosis, thus recapitulating the main features of the human BSCL phenotype14, 15, 16. Here, BSCL2 is linked to Berardinelli-Seip congenital lipodystrophy.