PSMA3 encodes the alpha-3 subunit of the 20S proteasome core complex, a critical component of the cellular protein degradation machinery 1. The protein functions as a structural constituent of the proteasome, participating in both ubiquitin-dependent degradation through the 26S proteasome and ubiquitin-independent proteolysis when associated with regulatory particles PA200 or PA28 1. PSMA3 demonstrates significant clinical relevance across multiple diseases. In cancer, particularly multiple myeloma, PSMA3 contributes to proteasome inhibitor resistance through exosomal transfer from mesenchymal stem cells, with higher plasma levels correlating with poorer progression-free survival and overall survival 2. The antisense long non-coding RNA PSMA3-AS1 forms RNA duplexes with pre-PSMA3 transcripts, stabilizing and promoting PSMA3 expression, which enhances drug resistance 2. PSMA3 has emerged as a diagnostic biomarker, identified as one of eight genes with diagnostic value for both Alzheimer's disease and metabolic syndrome 3. Additionally, PSMA3 deletions have been associated with undiagnosed rare diseases 4, and plasma PSMA3 levels change following long-term physical exercise, correlating with putative glymphatic flow improvements 5. These findings highlight PSMA3's dual roles in protein homeostasis and disease pathogenesis.