Lipid droplets are universal intracellular organelles composed of a triglyceride, cholesteryl ester and retinyl ester core, surrounded by a monolayer of phospholipids and free (unesterified) cholesterol and lipid droplet-associated proteins. Core lipids are hydrolyzed by lipases to provide fatty acids, cholesterol and retinol for various cellular functions. In addition to cytosolic adipose triglyceride lipase and hormone-sensitive lipase, recent studies show the existence of other neutral lipid hydrolases that reside in the endoplasmic reticulum. In this review we highlight the role of these novel lipases including several members of the carboxylesterase family and enzymes termed arylacetamide deacetylase and KIAA1363/neutral cholesteryl ester hydrolase1/arylacetamide deacetylase-like 1. Some of these enzymes might be attractive targets for the treatment of dyslipidemias, viral infection and atherosclerosis.
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