Aspartyl aminopeptidase (DAP), encoded by the DNPEP gene, is believed to be a cytosolic protein with high enzymatic activity in the neuroendocrine tissues. Bioinformatic analysis revealed that the genomic segment spanning the DNPEP gene is evolutionarily conserved from Caenorhabditis elegans to humans. In the present study, we sought to determine whether the expression of DAP is associated with its clustered genes when expressed in pancreatic islet cells. Using anti-DAP specific antibody in immunofluorescent stainings, we found that DAP was specifically expressed in islet alpha cells but not in exocrine acinar cells. Moreover, using electron microscopy, we found that DAP was associated with a lysosomal-like structure and secretory granules, suggesting that it plays an important role in post-translational processing and the secretion of hormones in islet cells. The identification and characterization of DNPEP syntenic genes confirm that conserved clustered genes can preferentially be expressed in the same signaling pathway.