Phenotypically, Casp2−/− mice have reduced maximal body weight, reduced body fat content and significantly reduced levels of subcutaneous adipose tissue11, 13 and are protected from diabetes-induced marrow adiposity.16 In addition, rat Casp2 increases in response to high-fat diet,17, 18 and human CASP2 is transcriptionally regulated by the sterol regulatory element binding proteins (SREBPs).19 Recently, it was suggested that Casp2 can initiate lipid induced apoptosis (lipoapoptosis) caused by saturated fatty acid-induced lipotoxicity.20, 21. This evidence concerns the gene CASP2 and diabetes mellitus.