The LH3 cDNA clones encode a 738-amino acid polypeptide, including a signal peptide of 24 residues. The overall amino acid sequence identity between the processed human PLOD3 and PLOD1 polypeptides is 59%, and that between the processed PLOD3 and PLOD2 polypeptides is 57%, whereas the identity to the processed Caenorhabditis elegans polypeptide is only 45%. All 4 critical residues at the catalytic site, 2 histidines, 1 aspartate, and 1 arginine, are conserved in all of these polypeptides. The mRNA for PLOD3 was found to be expressed in a variety of tissues, but distinct differences appeared to exist in the expression pattern of the 3 isoenzyme mRNAs. Recombinant PLOD3 expressed in insect cells by means of a baculovirus vector was found to be more soluble than PLOD1 expressed in the same cell type.