Dpep3, or dipeptidase 3, is one of three glycosylphosphatidylinositol-anchored metallopeptidases potentially involved in the hydrolytic metabolism of dipeptides [2]. Its mRNA is predominantly detected in testicular tissue in mice, and it is evolutionarily conserved among human, mouse, and other eutherians [1].

In a study using CRISPR/Cas9-generated Dpep3 knockout (Dpep3-/-) mice, male Dpep3-/-mice were found to be fertile despite a significant reduction in sperm count. Histology of the testis and progression of meiotic prophase I showed no obvious difference between wild-type and Dpep3-/-mice, indicating that Dpep3 is not essential for male fertility in mice [1]. Structurally, DPEP3 shares a conserved, dimeric TIM (β/α)8-barrel fold with DPEP1 and DPEP2 but diverges in key active-site positions, resulting in no in vitro dipeptidase activity against various substrates, suggesting it may require an activating co-factor in vivo or be an inactive, degenerate enzyme [2].

In conclusion, although Dpep3 is mainly expressed in the testis, its absence does not render male mice infertile. The study of Dpep3 knockout mice has provided insights into its non-essential role in male fertility. The unique structural features of DPEP3 also contribute to our understanding of the differences between active and inactive membrane dipeptidases [1,2].