PSMD1 encodes a non-ATPase subunit of the 26S proteasome complex that plays critical roles in protein degradation and cellular homeostasis 1. The protein serves as a structural component of the 19S regulatory particle, where it interacts with other proteasome subunits and regulatory proteins like TXNL1 to facilitate ubiquitin-dependent protein degradation 1. PSMD1 regulates cellular metabolism by modulating lipid droplet formation through p38-JNK and AKT signaling pathways, which supports tumor cell proliferation 2. The gene shows significant disease relevance, particularly in cancer progression. High PSMD1 expression correlates with poor prognosis in hepatocellular carcinoma and promotes tumor growth through the RTKN/β-catenin/PD-L1 axis 3. In multiple myeloma, proteasome subunit genes including PSMD1 are associated with proteasome inhibitor resistance 4. Environmental factors also affect PSMD1 function, as arsenic exposure leads to genetic polymorphisms and decreased expression, potentially increasing disease susceptibility 5. Clinically, PSMD1 depletion represents a promising therapeutic strategy for aggressive cancers, as reducing the 26S/20S proteasome ratio effectively inhibits tumor growth in xenograft models while sparing normal cells 6. Additionally, PSMD1 is part of prognostic gene signatures for hepatocellular carcinoma 7.