PSMA6 encodes the alpha-6 subunit of the 20S proteasome core complex, which functions as a critical component in protein degradation pathways 1. The protein participates in both ubiquitin-dependent protein degradation as part of the 26S proteasome complex and ubiquitin-independent degradation when associated with regulatory particles PA200 or PA28. Genetic variants in PSMA6, particularly the functional polymorphism rs1048990 (C/G) located in the 5' untranslated region, have been extensively studied for disease associations 2. Meta-analysis of 15,991 cases and 16,784 controls demonstrated that the G allele of this polymorphism significantly increases coronary artery disease risk (OR 1.09, 95% CI: 1.02-1.16), with stronger associations observed in East Asian populations compared to Caucasians 3. The variant shows protective effects against end-stage kidney disease (OR 0.34, 95% CI 0.26-0.45) but is associated with left ventricular hypertrophy in kidney disease patients 4. Additional studies have linked PSMA6 variants to type 2 diabetes mellitus 5 and juvenile idiopathic arthritis, particularly in sex-specific and subtype-specific patterns 6. The functional significance of these variants may involve altered transcription factor binding and proteasome expression levels 6.