PSMB8 encodes a catalytic beta subunit of the immunoproteasome, a specialized form of the 20S proteasome induced by interferon-γ that plays critical roles in antigen processing and cellular homeostasis 1. The immunoproteasome component PSMB8 is important for antigen-dependent immune editing of cancer cells 1. In cardiovascular disease, PSMB8 promotes vascular inflammation and atherosclerosis through the NONO/PSMB9/ZEB1 axis, with elevated levels found in human atherosclerotic plaques 2. In neurological contexts, PSMB8 has dual roles: interferon-γ-mediated induction impairs proteasomal balance, leading to metabolic disruption and neurodegeneration in multiple sclerosis 3, while upregulation occurs in dementia with Lewy bodies brains 4. However, PSMB8 also provides cardioprotection by targeting Drp1 degradation to inhibit mitochondrial fission during myocardial ischemia/reperfusion injury 5. Disease associations include proteasome-associated autoinflammatory syndromes caused by homozygous PSMB8 mutations 6, and its role as a therapeutic vulnerability in KMT2A-rearranged acute myeloid leukemia through maintenance of oncogenic gene expression 7. In gliomas, PSMB8 serves as a prognostic biomarker and promotes malignant phenotypes via TGF-β signaling activation 8.