Recent developments in understanding the biochemical and molecular nature of the CE hydrolases and their impact on cellular cholesterol trafficking have further defined the enzyme's mechanism of action with reasonable clarity. The availability of the cDNA probe for the human lysosomal acid lipase/CE hydrolase and the hormone-sensitive lipase now makes it possible to study CE hydrolase gene regulation and expression in human tissue; and it can now be stated with more assurance that the cytoplasmic CE hydrolase (NCEH) is most likely activated through phosphorylation by the cyclic AMP-dependent protein kinase. Evidence also shows that the NCEH is most likely identical to the hormone-sensitive lipase and that it plays an important role in cholesterol efflux properties of the cell. Recent advances in the discovery of the role of the eicosanoid/cytokine network in the regulation of CE hydrolysis, highlighted in Figure 10, further emphasize the interesting but complex nature of the cholesterol trafficking processes in cells, particularly under pathophysiological conditions such as cell injury, repair, and inflammation. It can be speculated that in several years, when the crystal structure of the CE hydrolase is known, the structure-function properties of this enzyme's catalytic domain, as it relates to the physical state of the CE substrates, should further clarify the precise role of this enzyme in intracellular cholesterol mobilization and trafficking under a variety of cellular conditions.