PSMB10 (proteasome 20S subunit beta 10) is an immunoproteasome catalytic subunit that functions as a core component of the 26S proteasome complex, characterized by its ability to cleave peptides at neutral or slightly basic pH 1. As an interferon-γ-regulated subunit, PSMB10 plays essential roles in antigen processing and MHC class I peptide generation, critical for CD8+ T-cell activation and immune surveillance 2. Mechanistically, PSMB10 maintains proteasomal protein degradation capacity and regulates cellular proteostasis. In acute myeloid leukemia (AML), PSMB10 is significantly upregulated (13-fold) in chemotherapy-resistant leukemia stem cells, where it inhibits senescence induction and cytotoxic T lymphocyte-mediated killing by preventing MHC-I protein degradation and blocking SLC22A16-mediated drug endocytosis 3. PSMB10 knockout substantially reduces drug-resistant leukemia stem cell frequency by 19-fold in human xenografts and impairs their stemness maintenance 3. Clinically, PSMB10 mutations cause severe combined immunodeficiency and Omenn syndrome through dominant-negative effects that reduce overall immunoproteasome expression, impairing CD8+ T-cell positive selection and generating diverse T-cell repertoires 2. Additionally, PSMB10 expression is upregulated in thymic carcinomas, which show sensitivity to proteasome inhibitors 4. Pathogenic variants in PSMB10 also associate with proteasome-associated autoinflammatory syndromes (PRAAS) presenting with elevated type I interferon responses 5. These findings identify PSMB10 as a therapeutic target for AML and immune disorders.