PSMB3 encodes a non-catalytic beta subunit of the 20S core proteasome complex that plays essential roles in intracellular protein degradation 1. As part of the 26S proteasome (formed with 19S regulatory particles), PSMB3 participates in ATP-dependent degradation of ubiquitinated proteins, while association with PA200 or PA28 enables ubiquitin-independent proteolysis 2. The gene shows developmental regulation, being overexpressed in blastocysts compared to oocytes, suggesting importance in early embryonic protein turnover and cell cycle control 3. PSMB3 expression is elevated in non-small cell lung cancer where it correlates with poor survival outcomes 1. Disease relevance includes potential involvement in neurodegenerative disorders, with Mendelian randomization studies identifying brain PSMB3 levels as potentially protective against amyotrophic lateral sclerosis risk 4. In rheumatoid arthritis patients with type 2 diabetes, reduced PSMB3 expression is associated with altered IL-1 pathway activity 2. Additionally, PSMB3 serves as an autoantigen in breast cancer, where autoantibodies against PSMB3 may function as diagnostic biomarkers 5. The protein's stability and expression are regulated by proteasome activity itself, demonstrating feedback regulation in cellular proteostasis 6.