PSMD8 is a non-ATPase component of the 26S proteasome regulatory particle that functions in ATP-dependent degradation of ubiquitinated proteins 1. As part of the proteasome complex, PSMD8 participates in protein homeostasis by removing misfolded, damaged, or functionally obsolete proteins, thereby maintaining cellular functions and supporting processes including cell cycle progression, apoptosis, and DNA damage repair 1. In cancer pathology, PSMD8 is significantly overexpressed in ovarian cancer tissues and associated with poor prognosis, enhanced tumor cell proliferation, migration, and invasion 2. Similarly, PSMD8 is upregulated in breast cancer and triple-negative breast cancer, identified as a hub gene involved in proteasomal protein degradation pathways 34. PSMD8 upregulation is also observed in age-related macular degeneration, where it participates in proteasome-mediated polyubiquitination during retinal pigment epithelial senescence 5. Beyond cancer, PSMD8 plays roles in broader metabolic regulation; DNA methylation at a PSMD8-associated locus correlates with circulating adiponectin levels in African populations, suggesting involvement in lipid metabolism and proteostasis pathways affecting cardiometabolic health 6. In osteoarthritis, PSMD8 emerges as one of 15 diagnostic biomarkers with high discriminatory power (AUC > 0.7) 7. These findings establish PSMD8 as a potential therapeutic target and diagnostic/prognostic biomarker across multiple disease contexts.