Endothelial lipase (EL), a new member of the lipase gene family, was recently cloned and has a significant role in plasma high-density lipoprotein levels (HDL). EL has a highly similar molecular homology to lipoprotein lipase and hepatic lipase. It is synthesized by endothelial cells and functions at the cell surface. EL primarily has phospholipase A1 activity. Animals that overexpress EL showed decreased HDL cholesterol levels and those that lack EL show elevated levels of HDL cholesterol. The expression is highly regulated by cytokines and physical forces. These data suggest that EL may play a significant role in atherosclerosis.