Dpp3, also known as dipeptidyl peptidase 3 and NEMP3 (neuron bound extracellular metallopeptidase 3), is a zinc-dependent peptidase [3]. It contains the unique HEXXGH catalytic sequence and is mainly cytoplasmic, associated with the degradation of oligopeptides having 4 to 10 amino acid residues [1]. Dpp3 is involved in various cellular activities and pathophysiological mechanisms, such as the renin-angiotensin system (related to blood pressure regulation), pain signaling, inflammation, and oxidative stress [1].

In cardiovascular diseases, Dpp3 serves as a biomarker for poor prognosis in patients, with plasma Dpp3 concentration levels closely linked to the mortality of diseases like cardiogenic shock and heart failure [1]. In cardiogenic shock patients, higher circulating Dpp3 (cDPP3) plasma concentration was associated with the need for ventilation, pulmonary hypertension, and reduced stroke volume, suggesting its potential to predict disease progression [6].

In cancer, Dpp3 is upregulated in breast, esophageal, and colorectal cancers. In breast cancer, Dpp3 promotes tumorigenesis by stabilizing FASN and promoting lipid synthesis [2]. In esophageal carcinoma, Dpp3 depletion led to reduced cell proliferation, migration, and enhanced apoptosis, inhibiting tumour growth and invasion in a xenograft model [4]. In colorectal cancer, down-regulation of Dpp3 inhibited cell proliferation, colony formation, migration, and promoted apoptosis in vitro and reduced tumorigenicity in vivo, and it was found to target CDK1 [5].

In conclusion, Dpp3 plays significant roles in both cardiovascular diseases and cancer. In cardiovascular diseases, it has potential as a biomarker for cardiogenic shock progression. In cancer, it acts as an oncogene-like factor promoting tumour development in multiple cancer types. These findings from functional studies, including those resembling gene-knockout-like effects in cell models, help in understanding its biological functions and its potential as a therapeutic target in these disease areas.