PSMB5 encodes the beta-5 subunit of the 20S proteasome core complex, which exhibits chymotrypsin-like proteolytic activity essential for protein degradation 1. The protein functions within both the 26S proteasome (for ubiquitin-dependent degradation) and 20S-PA28/PA200 complexes (for ubiquitin-independent proteolysis) 1. PSMB5 can be displaced by the immunoproteasome subunit LMP7 upon interferon-gamma stimulation, altering proteolytic specificity for antigen presentation 2. The gene maps to chromosome 14 and contains three exons spanning approximately 5 kilobases 2. Clinically, PSMB5 overexpression correlates with poor prognosis in hepatocellular carcinoma, where it promotes cell proliferation and migration through the PI3K/Akt/mTOR pathway 3. In rheumatoid arthritis, mitochondrial dysfunction leads to reduced PSMB5 transcription via BRD2 succinylation, contributing to abnormal tissue-resident memory T cell differentiation 4. PSMB5 also serves as a target for proteasome inhibitor therapy in multiple myeloma, though resistance can develop through epigenetic silencing of related proteasome subunits 5. Additionally, PSMB5 represents a potential therapeutic target in bladder cancer, where its expression is associated with PANoptosis regulation 6.