Schistosomes rely on host hemoglobin (Hb) degradation for acquiring essential amino acids for growth and sexual maturation. Proteases involved in Hb catabolism are therefore considered as a priori targets for developing antischistosomal drugs. The first aspartyl protease (AP) gene identified in Schistosoma mansoni (SmCD1) is homologous to mammalian cathepsin D and the encoded enzyme is able to hydrolyze human Hb. Transcriptome analysis of the parasite revealed that other AP genes are expressed in some life cycle stages. In this work we describe a second cathepsin D-like aspartyl proteinase gene from S. mansoni (SmCD2). We employed 5'- and 3'-RACE (rapid amplification of cDNA ends) technique to obtain the complete coding sequence of SmCD2 (1152 bp), the second most abundant transcript (as judged by the number of ESTs deposited in databases) encoding an AP gene in S. mansoni. A Blast search in the public S. mansoni genome database indicates that SmCD2 gene preserves the basic genomic organization found for SmCD1 gene with seven exons. SmCD2 protein shares 62% identity with SjCD2, the orthologous gene from Asiatic schistosome species (S. japonicum) while it holds 46% and 41% identity to SmCD1 and human cathepsin D, respectively. SmCD2 is predicted to have four N-glycosylation sites, none of which are conserved in SmCD1 while two of them are found in the pro-part (N32 and N43). Indeed, sequence alignment revealed that the SmCD2 pro-peptide is considerably distinct from SmCD1 indicating that a different activation mechanism may take place within these proteases. From analysis of a homology 3D model we propose that SmCD2 may show different substrate specificity from SmCD1 since many residues delimiting the predicted substrate binding cleft are mutated to present distinct physicochemical properties. Following RT-PCR using gene-specific primers with adult mRNA we have amplified and cloned the SmCD2 fragment encoding the putative pro-enzyme. Finally, we have subcloned proSmCD2 in pET28a vector and are currently performing expression tests in Escherichia coli aiming to produce large quantities of this protease for future immunological, structural  and functional studies.