DNPEP (aspartyl aminopeptidase) is a cytosolic metallopeptidase with specificity for acidic amino acids at the N-terminus of protein substrates 1. The enzyme functions as a dodecameric complex utilizing a binuclear zinc center for catalysis 1. DNPEP plays critical roles in intracellular protein and peptide metabolism, including regulation of angiotensin II signaling 2. In breast cancer, DNPEP acts as a tumor suppressor through multiple mechanisms. DNPEP expression is significantly downregulated in breast cancer tissues, and overexpression suppresses cell proliferation, migration, and invasion 3. Mechanistically, DNPEP promotes CD44 degradation via its hydrolase activity, reducing cancer stemness properties 3. DNPEP is phosphorylated by PAK5 at serine 119, and this phosphorylation regulates DNPEP-mediated degradation of USP4, a deubiquitinase that promotes metastasis 4. Clinical evidence shows DNPEP downregulation correlates with poor breast cancer survival 4, and elevated FBXO3-USP4-Twist1 axis expression (which inhibits DNPEP function) predicts worse outcomes 5. Beyond breast cancer, DNPEP was identified as a gene disfavoring T cell immunity against tumors, suggesting therapeutic potential when combined with adoptive T cell therapy 6. Selective DNPEP inhibitors have been developed as research tools to study enzyme physiology 2, and DNPEP-activated nanoparticles show promise for tumor imaging and photothermal/photodynamic therapy 7.