Recent achievement on the molecular cloning of various ganglioside synthtase genes as well as the development of ganglioside biosynthesis inhibitor (D-PDMP) and accelerator (L-PDMP) leads us the new dimension for the elucidation of the physiological function of gangliosides. Based on these remarkable progress, we could demonstrate here that 1) The anti-apoptotic action of L-PDMP in neuronal cells may be the specific binding ability of this ceramide analog to voltage-dependent anion channel (VDAC) protein. Since VDAC localizes the mitochondrial outer membrane and regulates the release of cytochrome C (an executor of apoptosis through mitochondria), further study to elucidate the inhibitory mechanism of VDAC function by L-PDMP will open a new strategy for anti-apoptotic therapy.; 2) Acquisition of a state of insulin resistance in adipocytes induced by TNF-α may depend upon increased GM3 biosynthesis through upregulation of GM3 synthase gene expression. Pharmacological depletion of GM3 in adipocytes by D-PDMP prevented the TNF-α-induced defect in insulin-dependent signaling. The increased synthesis of cellular GM3 by TNF may participate in the pathological conditions of insulin resistance in type 2 diabetes.