Sphingolipids and their metabolism in physiology and disease

Sphingolipids are a major class of lipids, comprising various species with diverse functions. In addition to being structural elements of membranes, many sphingolipids are bioactive and regulate a myriad of cellular processes. Recent advances have shed new light on the complexity of sphingolipid metabolism and their various roles in physiology and disease. Studies of bioactive lipids in general and sphingolipids in particular have intensified over the past several years, revealing an unprecedented and unanticipated complexity of the lipidome and its many functions, which rivals, if not exceeds, that of the genome or proteome. These results highlight critical roles for bioactive sphingolipids in most, if not all, major cell biological responses, including all major cell signalling pathways, and they link sphingolipid metabolism to key human diseases. Nevertheless, the fairly nascent field of bioactive sphingolipids still faces challenges in its biochemical and molecular underpinnings, including defining the molecular mechanisms of pathway and enzyme regulation, the study of lipid–protein interactions and the development of cellular probes, suitable biomarkers and therapeutic approaches.