Dysfunctional sphingolipid metabolism in the diabetic retina, with an increase in SC ceramides due to pathological activation of ASM and a decrease in VLC ceramides due to downregulation of ELOVL4-mediated production of VLC saturated fatty acids, is an important metabolic insult contributing to the development of DR (50, 51, 52, 106, 107). This evidence concerns the gene ELOVL4 and diabetes mellitus.