PSMA4 encodes proteasome 20S subunit alpha 4, a structural component of the 20S core proteasome complex that degrades intracellular proteins. The protein functions as part of both ubiquitin-dependent (26S proteasome) and ubiquitin-independent proteolytic pathways, playing essential roles in protein homeostasis 1. PSMA4 demonstrates critical regulatory mechanisms in disease contexts. In cancer, lactylation of PSMA4 at lysine residues facilitates degradation of cGAS (cyclic GMP-AMP synthase) through ubiquitin-independent proteasomal degradation, with phosphorylation of PSMA4 S188 disrupting this association and affecting tumor growth 1. The protein shows significant clinical relevance across multiple diseases. Mendelian randomization studies have identified PSMA4 as a potential therapeutic target for chr15 obstructive pulmonary disease, with the drug MARIZOMIB targeting PSMA4 potentially reducing COPD risk 2. Similarly, PSMA4 inhibition may reduce aortic aneurysm risk 3 and shows associations with osteoporosis through immune-related protein degradation pathways 4. In multiple myeloma, PSMA4 overexpression facilitates bortezomib resistance by inducing metabolic reprogramming and activating HIF-1α signaling 5. Additionally, PSMA4 genetic variants influence non-small cell lung cancer survival outcomes 6.