Dpep1, also known as Dipeptidase-1, is a zinc-dependent metalloproteinase. It functions as a major neutrophil adhesion receptor and is involved in leukocyte recruitment. It may play a role in pathways related to inflammation, ferroptosis, and tumor-related signaling such as PI3K/Akt/mTOR [1,4-7]. It is of great biological importance in processes like renal function, cancer development, and immune cell-mediated inflammation. Genetic models, especially KO mouse models, have been crucial in studying its functions.

In renal ischemia reperfusion injury (IRI), Dpep1-/-mice showed attenuated renal inflammation and acute kidney injury (AKI) phenotypes. Dpep1 deficiency primarily blocked neutrophil adhesion to peritubular capillaries and reduced inflammatory monocyte recruitment to the kidney after IRI [1]. In colon cancer cells, interfering with the positive feedback loop between Dpep1 and ASCL2 could potentially reverse drug resistance [2]. In hepatoblastoma, silencing Dpep1 in vitro and in vivo significantly suppressed cell proliferation, migration, and invasion [3]. In B cell acute lymphoblastic leukaemia, high Dpep1 transcript levels were associated with increased relapse and Dpep1 promoted cell proliferation and survival [4].

In conclusion, Dpep1 plays essential roles in inflammation-related processes like neutrophil and monocyte recruitment in the kidney during IRI, as well as in cancer-related processes such as drug resistance in colon cancer, tumor cell progression in hepatoblastoma, and leukaemia cell proliferation and survival. The use of Dpep1 KO mouse models has been instrumental in revealing these functions, providing insights into potential therapeutic targets for diseases like AKI and various cancers.