Dpp4, also known as dipeptidyl peptidase 4 or CD26, is a type II transmembrane protein and serine protease. It selectively degrades various substrates like incretin hormones, growth factors, and cytokines. Dpp4 is involved in multiple biological processes including inflammation, immune regulation, cell growth, migration, and differentiation, and is associated with metabolic, cardiovascular, and age-related disease pathways [3,4]. Genetic models, such as gene knockout (KO) mouse models, are valuable for studying its functions.

In genetic studies, the deletion of Dpp4 in rodents protected them from developing insulin resistance and improved cardiovascular outcomes, suggesting Dpp4 may be a key link between central obesity, insulin resistance, and atherosclerosis [1]. In a study on calcific aortic valve disease (CAVD), DUSP26 promoted aortic valve calcification by inhibiting Dpp4 degradation, indicating a role for Dpp4 in this disease process [2].

In conclusion, Dpp4 has pleiotropic functions in various biological processes and disease conditions. KO mouse models have revealed its role in insulin resistance, cardiovascular outcomes, and aortic valve calcification. Understanding Dpp4's functions through these research models provides insights into the mechanisms of related diseases and may offer potential therapeutic targets.

References:

1. Love, Kaitlin M, Liu, Zhenqi. . DPP4 Activity, Hyperinsulinemia, and Atherosclerosis. In The Journal of clinical endocrinology and metabolism, 106, 1553-1565. doi:10.1210/clinem/dgab078. https://pubmed.ncbi.nlm.nih.gov/33570554/

2. Wang, Yongjun, Han, Dong, Zhou, Tingwen, Cao, Feng, Dong, Nianguo. . DUSP26 induces aortic valve calcification by antagonizing MDM2-mediated ubiquitination of DPP4 in human valvular interstitial cells. In European heart journal, 42, 2935-2951. doi:10.1093/eurheartj/ehab316. https://pubmed.ncbi.nlm.nih.gov/34179958/

3. Sun, Lu, Ma, Yuhui, Geng, Chenchen, Zhu, Shuzhen, Zhang, Ping. 2025. DPP4, a potential tumor biomarker, and tumor therapeutic target: review. In Molecular biology reports, 52, 126. doi:10.1007/s11033-025-10235-6. https://pubmed.ncbi.nlm.nih.gov/39821530/

4. Nargis, Titli, Chakrabarti, Partha. 2018. Significance of circulatory DPP4 activity in metabolic diseases. In IUBMB life, 70, 112-119. doi:10.1002/iub.1709. https://pubmed.ncbi.nlm.nih.gov/29331088/