[Research progress on multidimensional biological functions and targeted intervention strategies of dipeptidyl...

Dipeptidyl peptidase 4 (DPP4) is a membrane-anchored protein ubiquitously expressed across various cell types, primarily responsible for cleaving N-terminal X-Pro or X-Ala dipeptides from polypeptides. It plays a crucial role in glucose metabolism by degrading incretin hormones, thereby regulating blood glucose homeostasis and establishing itself as a key therapeutic target for type 2 diabetes mellitus. In addition, DPP4 has emerged as a potential biomarker and intervention target in pathologies such as fibrosis, inflammation, and cancer. In terms of therapeutic strategies, in addition to conventional small-molecule inhibitors, DPP4-inhibitory peptides have shown significant efficacy in vitro, underscoring their potential for the control of high blood glucose. Advancements in the development of DPP4-specific antibodies are creating new opportunities for diagnosing and treating DPP4-related diseases. This review systematically delineates the established enzymatic functions and blood glucose-rising mechanisms of DPP4, its novel pathological roles in fibrotic, inflammatory, and oncological processes, and discusses recent progress in diverse intervention strategies, including small molecules, inhibitory peptides, and antibodies. It helps deepen the overall understanding of the multifaceted biological functions of DPP4 and its associations with disease, and provides a theoretical basis for optimizing DPP4-targeted therapeutic strategies and developing novel treatment approaches.