PSMA2 (proteasome 20S subunit alpha 2) is a core catalytic component of the 20S proteasome complex, which functions as the central hub of the ubiquitin-proteasome system (UPS) for intracellular protein degradation 1. When associated with 19S regulatory particles, PSMA2 forms the 26S proteasome, enabling ATP-dependent degradation of ubiquitinated proteins and maintaining cellular protein homeostasis by removing misfolded or damaged proteins 1. PSMA2 also participates in ubiquitin-independent proteolysis when associated with PA200 or PA28 regulatory particles, supporting specialized processes including spermatogenesis and MHC class I antigen presentation 1. Beyond canonical proteasomal function, PSMA2 dysregulation has emerged as a key factor in multiple diseases. PSMA2 is significantly upregulated in gliomas, where it promotes tumor proliferation and migration through epithelial-mesenchymal transition (EMT) and correlates with advanced tumor stages and poor survival 2. Similarly, elevated PSMA2 expression in type 2 diabetes-related cervical cancer is associated with increased proliferation, and Exendin-4 treatment reduces PSMA2 expression via NF-κB pathway inhibition 3. PSMA2 upregulation also appears in ovarian cancer, contributing to chemoresistance and poor prognosis 4. Pathogen studies reveal PSMA2's role in viral evasion: influenza A virus hijacks PSMA2 to suppress the NRF2-mediated antioxidant response, facilitating viral maturation and immune evasion 5, while PSMA2 acts as a restriction factor limiting Zika virus replication in astrocytic cells 6. In pancreatic fibrosis, PSMA2 inhibition by corynoline alleviates disease progression 7, while proteasome-targeting antioxidants downregulate PSMA2 in endothelial cells 8. PSMA2 knockdown broadly dysregulates immune and stress response pathways 1, highlighting its multi-functional importance in cellular homeostasis and disease pathogenesis.