17 beta-Hydroxysteroid dehydrogenase (17 beta HSD) type 13 is identified as a new lipid droplet-associated protein. 17 beta HSD type 13 has an N-terminal sequence similar to that of 17 beta HSD type 11, and both sequences function as an endoplasmic reticulum and lipid droplet-targeting signal. Localization of native 17 beta HSD type 13 on the lipid droplets was confirmed by subcellular fractionation and Western blotting. In contrast to 17 beta HSD type 11, however, expression of 17 beta HSD type 13 is largely restricted to the liver and is not enhanced by peroxisome proliferator-activated receptor alpha and its ligand. Instead the expression level of 17 beta HSD type 13 in the receptor-null mice was increased several-fold. 17 beta HSD type 13 may have a distinct physiological role as a lipid droplet-associated protein in the liver. (C) 2008 Elsevier Inc. All rights reserved.