PSMA1 (proteasome 20S subunit alpha 1) is a core catalytic component of the 20S proteasome complex, which functions as the proteolytic engine of the ubiquitin-proteasome system. As part of the 26S proteasome, PSMA1 participates in ATP-dependent degradation of ubiquitinated proteins, maintaining cellular protein homeostasis by removing misfolded, damaged, or functionally obsolete proteins [UniProt]. The 20S complex can also associate with regulatory particles PA200 or PA28 to mediate ubiquitin-independent proteolysis required for processes including spermatogenesis and MHC class I antigen presentation [UniProt]. Beyond canonical proteasomal degradation, PSMA1 exhibits unexpected deubiquitinase activity. In gastric carcinoma, PSMA1 directly interacts with and stabilizes the oncogenic transcriptional co-activator TAZ through deubiquitination, promoting tumor cell proliferation, migration, and invasion 1. This non-canonical function contributes to poor clinical prognosis. Clinically, PSMA1 is significantly upregulated across multiple human malignancies. In oral squamous cell carcinoma and lung squamous cell carcinoma, elevated PSMA1 expression correlates with advanced clinicopathological features, reduced overall survival, and serves as an independent poor prognostic factor [PMID:38216818; 23]. In prostate cancer, PSMA1-mediated signaling through the NF-κB-HIF-1α axis promotes tumor-associated neutrophil trap secretion, facilitating disease progression 3. These findings position PSMA1 as both a therapeutic target and potential biomarker for cancer management.