PSME3 (proteasome activator subunit 3) is a key component of the 11S proteasome regulator that modulates proteasomal degradation and exhibits diverse cellular functions. As a proteasome activator, PSME3 enhances trypsin-like catalytic activity while inhibiting chymotrypsin-like activity 1. The protein plays critical roles in immune responses, including bacterial defense through generation of antimicrobial peptides, where bacterial infection induces PSME3 recruitment and increased tryptic-like cleavage 1. PSME3 significantly impacts immune regulation by modulating cytokine production and NF-κB signaling in macrophages, with reduced expression correlating with increased susceptibility to Staphylococcus aureus infection 2. In cancer biology, PSME3 functions as an oncogene across multiple tumor types, promoting cell proliferation, metabolic reprogramming toward glycolysis, and treatment resistance 345. Mechanistically, PSME3 stabilizes oncogenic proteins like c-Myc and enhances PTEN degradation through FBXL7-mediated ubiquitination 65. Clinically, elevated PSME3 expression correlates with poor prognosis in various cancers including hepatocellular carcinoma, pancreatic cancer, and gastric cancer, while also contributing to radioresistance and immune evasion 76. Additionally, PSME3 plays roles in pregnancy-related disorders, where its downregulation contributes to severe preeclampsia through increased trophoblast apoptosis 8.