PSMG4 is a proteasome assembly chaperone that promotes the assembly of the 20S proteasome core complex through chaperoning of proteasomal α subunits 1. It functions as part of a PAC3-PAC4 heterodimer that acts as a molecular matchmaker, stabilizing intermediate subcomplexes during proteasome assembly and ensuring proper arrangement of α subunits essential for proteasomal function 1. In disease contexts, PSMG4 expression is significantly elevated in lung adenocarcinoma tissues compared to normal lung, and this elevated expression correlates with poor patient prognosis 2. PSMG4 knockdown in lung cancer cells decreases cell proliferation, suggesting its role in tumor progression 2. Additionally, PSMG4 variants (p.W99R) have been identified as genetic modifiers associated with multiple sclerosis disease severity and earlier age at clinical onset 3. Genome-wide CRISPR screening identified PSMG4 among genes conferring sensitivity to colibactin-induced DNA damage, a genotoxin implicated in colorectal cancer development 4. These findings establish PSMG4 as both a critical proteasome biogenesis factor and an emerging prognostic biomarker with potential therapeutic implications in cancer and neuroinflammatory diseases.