DPEP3 (dipeptidase 3) is a glycosylphosphatidylinstitial-anchored membrane protein normally expressed in testis 1 that lacks enzymatic dipeptidase activity, distinguishing it from related DPEP1/2 enzymes 1. Structural analysis reveals DPEP3 contains critical amino acid substitutions: asparagine at position 359 (instead of aspartate in active enzymes) prevents activation of the catalytic water/hydroxide, while tyrosine at position 269 (versus histidine) reduces β-zinc affinity and causes substrate steric hindrance 1. Consequently, DPEP3 cannot hydrolyze typical dipeptidase substrates including cystinyl-bis-glycine, leukotriene D4, or the β-lactam antibiotic imipenem 1. Biologically, DPEP3 functions as a testis-specific cell-surface protein that forms a complex with TEX101, a cell-surface chaperone regulating spermatozoa maturation 2. However, DPEP3 knockout mice remain fertile despite reduced sperm counts, indicating it is non-essential for male fertility 3. Clinically, DPEP3 expression is upregulated in platinum-resistant ovarian cancer and serves as a target for antibody-drug conjugates in cancer immunotherapy 45. DPEP3 is also expressed in non-small cell lung cancer as a cancer-testis antigen 6. These findings suggest DPEP3 functions primarily as a structural or regulatory protein rather than a catalytic enzyme.