PSMA5 encodes the α5 subunit of the 20S core proteasome, a critical component of the ubiquitin-proteasome system responsible for intracellular protein degradation 1. The protein forms part of the outer α-subunit rings that bind proteasome regulators and activators, with the refolded human PSMA5 existing primarily as a tetramer 2. PSMA5 participates in both ubiquitin-dependent protein degradation as part of the 26S proteasome complex and ubiquitin-independent degradation when associated with PA200 or PA28 regulatory particles 1. The gene shows significant disease relevance, with upregulation observed in lung adenocarcinoma where it promotes tumor progression through JAK/STAT pathway activation, correlating with poor prognosis and lymph node metastasis 3. Similarly, PSMA5 promotes tumorigenic processes in prostate cancer and is associated with bortezomib resistance 4. In glioblastoma, PSMA5 modulates cellular senescence and tumor growth, serving as both a prognostic biomarker and potential therapeutic target 5. Novel pathogenic variants in PSMA5 have been identified in proteasome-associated autoinflammatory syndromes (PRAAS), expanding the genetic spectrum of these conditions 6. These findings establish PSMA5 as clinically significant in cancer progression and inflammatory diseases.