A view on sphingolipids and disease

Sphingolipid and glycosphingolipid levels and expression of sphingolipid metabolizing enzymes are altered in a variety of diseases or in response to drug treatment. Inherited defects of enzymes and other proteins required for the lysosomal degradation of these lipids lead to human sphingolipidoses. Also genetic defects that affect sphingolipid biosynthesis are known. Although the molecular details are often far from clear, (glyco)sphingolipids have been implicated to play a role in atherosclerosis, insulin resistance, cancer, and infections by pathogens. More general aspects of selected diseases are discussed.

► Pathogenesis of sphingolipidoses is determined by the cell type-specific expression of sphingolipids and glycosphingolipids. ► Sphingolipid biosynthesis is affected only in few genetic disease. ► Glycosphingolipid levels can influence atherosclerosis, insulin resistance, cancer, and infections by pathogens.