PSMD11 is a non-ATPase regulatory subunit of the 26S proteasome complex that plays critical roles in protein homeostasis and cellular function. As a component of the proteasome lid subcomplex, PSMD11 is essential for proteasome assembly and enhanced activity, particularly in embryonic stem cells where its high expression promotes increased 26S proteasome assembly 1. The protein regulates circadian clock function through modulation of PER and CRY nuclear translocation, affecting the relative abundance of circadian repressors in the nucleus 2. PSMD11 can be phosphorylated by PKA at Ser14, which activates proteasome function and promotes degradation of misfolded proteins 3. Loss-of-function variants in PSMD11 cause neurodevelopmental proteasomopathies characterized by early-onset syndromic intellectual disability, neurodevelopmental delay, and recurrent obesity, resulting from impaired 26S proteasome assembly and persistent type I interferon signaling 1. In cancer contexts, PSMD11 is overexpressed in hepatocellular carcinoma where it promotes proliferation by regulating CDK4 ubiquitination and stability 45, and serves as a prognostic biomarker in severe fever with thrombocytopenia syndrome, correlating with viral load and organ dysfunction 6. PSMD11 also influences inflammatory responses in glomerular mesangial cells through NF-κB signaling regulation 7.