Dpp4, also known as CD26, is a type II transmembrane protein and exopeptidase. It selectively degrades various substrates like incretin hormones, growth factors, and cytokines. Dpp4 is involved in multiple processes such as inflammation, immune regulation, cell growth, migration, and differentiation, and is thus of great biological importance [3,4]. Genetic models, like KO/CKO mouse models, can be valuable for studying its functions.

In genetic deletion mouse models, Dpp4 deficiency protects rodents from developing insulin resistance and improves cardiovascular outcomes. Hyperinsulinemia promotes atherosclerosis, and Dpp4 mirrors its atherogenic actions in insulin-resistant states. DPP4 inhibition in pro-atherosclerotic preclinical models reduces inflammation, oxidative stress, improves endothelial function, and decreases atherosclerosis [1]. Also, in the context of hepatocellular carcinoma, HMGCL-induced β-hydroxybutyrate production affects Dpp4 expression, leading to HCC cells' vulnerability to ferroptosis [2].

In conclusion, Dpp4 plays essential roles in metabolism-related processes like insulin resistance and atherosclerosis, as well as in cancer-related processes such as hepatocellular carcinoma. Gene knockout models in rodents have been crucial in revealing Dpp4's role in these disease areas, providing insights into its functions and potential as a therapeutic target.