Ceramide and sphingolipids have received heightened attention in the past decade because of the recognition of their emerging roles in cell regulation. However, the understanding of these functions has been limited by a lack of complete understanding of the metabolism of sphingolipids, its subcellular localization and topography, binding targets and the requirement for highly sensitive analytical methods. Fortunately, rapid progress has occurred in the very recent past through the development and application of molecular cloning, mass spectrometric methods for qualitative/quantitative analysis, enzymology, RNA interference, chemical biology, and other approaches that have resulted in an explosion in understanding of these pathways. This review summarizes and critically evaluates these developments and how these new sets of tools can be applied to advance cell biology through lipid research.

The article describes new tools, new evidences, and new discoveries related to a lipid molecule, ceramide, and how it functions as a signal in the cell to coordinate the responses of cells to various stress stimuli. The nature and outcome of this ceramide signal is integral to the decision a cell makes to continue to live or die (controlled self-destruction). Failure to generate the signal can result in cells that survive and grow when they should not, as happens in cancer cells that resist deadly environments or attempts at killing them. Alternatively, overproduction of this lipid signal can result in premature death of cells including nerve cells in several neurodegenerative disorders such as in Alzheimer's disease.