PSMC2 (proteasome 26S subunit, ATPase 2) is a critical component of the 26S proteasome complex that functions as an ATPase to unfold ubiquitinated proteins for degradation. As part of the heterohexameric AAA+ ring, PSMC2 facilitates protein unfolding and translocation into the proteolytic chamber for peptide degradation, maintaining cellular protein homeostasis. The protein is overexpressed across multiple cancer types, including glioma 1, breast cancer 2, hepatocellular carcinoma 3, oral squamous cell carcinoma 4, and osteosarcoma 5. PSMC2 promotes oncogenesis through multiple mechanisms: it enhances cell proliferation and suppresses apoptosis by regulating the p21/cyclin D1 pathway 3, modulates the PI3K/AKT/mTOR signaling pathway 6 4, and influences the tumor immune microenvironment by promoting immunosuppressive cell infiltration 6. In cancer cells, PSMC2 knockdown significantly inhibits proliferation, promotes apoptosis, and reduces migration and invasion capabilities 1 2 5. High PSMC2 expression correlates with poor prognosis across multiple cancer types, making it a potential therapeutic target. Additionally, epigenetic silencing of proteasome subunits like PSMD5 through hypermethylation represents a mechanism of proteasome inhibitor resistance in multiple myeloma 7.