PSMD10 (proteasome 26S subunit, non-ATPase 10) functions as a proto-oncoprotein that negatively regulates key tumor suppressors. It facilitates degradation of retinoblastoma protein (RB1) by competing with CDKN2A for CDK4 binding and promotes p53 ubiquitination by enhancing MDM2 interactions, thereby targeting p53 for proteasomal degradation. PSMD10 also regulates nuclear factor-kappa-B by retaining RELA in the cytoplasm and mediating its nuclear export, counteracting TNF-α-induced apoptosis in cancer cells 1. Overexpression is associated with poor prognosis across multiple malignancies including multiple myeloma, hepatocellular carcinoma, cholangiocarcinoma, papillary thyroid carcinoma, and prostate cancer. In multiple myeloma treated with bortezomib, lenalidomide, and dexamethasone (VRD), high PSMD10 expression independently predicted shorter time to progression and progression-free survival 2. Therapeutic approaches targeting PSMD10 are emerging; doxorubicin has been identified as a first-generation small-molecule inhibitor that binds a vulnerable pocket on PSMD10 3. MicroRNA-mediated suppression of PSMD10 (via miR-214, miR-605, and miR-3619-5p) reduces cancer cell proliferation, migration, and invasion across multiple tumor types 4, 5, 6. Additionally, PSMD10 knockdown in multiple myeloma cells increases apoptosis 7, suggesting RNAi-based strategies as potential therapeutic avenues.