PSMD2 is a non-ATPase regulatory subunit of the 26S proteasome that serves as a critical component in both ubiquitin-dependent and ubiquitin-independent protein degradation pathways 1 2. The protein functions as a receptor that binds to substrates and facilitates their degradation through the proteasome complex. PSMD2 interacts with the midnolin ubiquitin-like domain and positions substrate-carrying domains above the proteasome ATPase channel for translocation and degradation 1 2. Additionally, PSMD2 can bind to nuclear localization sequences, confining certain proteolytic activities to the nucleus 2. In cancer contexts, PSMD2 is significantly overexpressed in hepatocellular carcinoma and correlates with poor prognosis 3. The protein promotes cancer cell proliferation by regulating cellular lipid droplet metabolism through p38-JNK and AKT signaling pathways 4. PSMD2 also shows positive correlation with immune checkpoint genes including PD1, PD-L1, and CTLA-4, and is associated with increased immune evasion potential and poor immunotherapy response 3. These findings suggest PSMD2 represents a promising therapeutic target and potential biomarker for cancer treatment, particularly in hepatocellular carcinoma.