Abstract : The very long chain fatty acids, synthesized by a microsomal chain-elongating enzyme system known as the elongase, are essential components of many cellular lipids. Each cycle of elongation involves four successive enzymatic reactions: condensation, reduction, dehydration, and a second reduction, and lengthens the fatty acid by 2 carbon units. Several enzymes that mediate condensation, including the soluble fatty acid synthases and the FAE1-like 3-ketoacyl-CoA synthases (FAE-KCSs) possess a catalytic triad of Cys, His, and His/Asn. In contrast, the Elop proteins, which are implicated in the condensation reaction lack any homology to the well-characterized condensing enzymes. There are three Elop proteins (Elo1p, Elo2p and Elo3p) in yeast and our in vitro assays with microsomes from wild type and the single elo mutants (elo1 delta, elo2 delta and elo3 delta) demonstrate that the Elops are essential for condensation.