Senp3, short for SUMO-specific protease 3, is a crucial enzyme involved in the de-SUMOylation process. SUMOylation is a protein modification process, and Senp3's function in reversing this modification influences the function, localization, stability, and interactions of proteins, regulating various cellular processes such as cell growth, DNA repair, and signaling pathway regulation [3].

In dendritic cells, DC-specific deletion of Senp3 drives tumor progression by blunting STING-dependent type-I interferon signaling and dampening antitumor immune responses, indicating its importance in STING-mediated antitumor immunity [1]. Macrophage-specific Senp3 knockout promotes M2 macrophage polarization and breast cancer progression, as loss of Senp3 enhances Akt1 SUMOylation, leading to its hyper-phosphorylation and activation [2]. Myeloid-specific Senp3 knockout inhibits abdominal aortic aneurysm (AAA) formation, with Senp3-mediated CTH deSUMOylation regulating macrophage ferroptosis and AAA development [4]. Also, in esophageal squamous cell carcinoma (ESCC), loss of Senp3 enhances macrophage alternative activation by mediating IRF4 de-SUMOylation, promoting ESCC cell migration, invasion, and in vivo progression [5].

In conclusion, Senp3 plays essential roles in multiple biological processes, especially in immune-related cell functions and cancer-related events. Gene knockout mouse models, including DC-specific, macrophage-specific, and myeloid-specific knockout models, have significantly contributed to understanding Senp3's functions in tumor progression, macrophage polarization, and aortic aneurysm development. These findings highlight Senp3 as a potential therapeutic target and biomarker in relevant disease areas.