PSMD13 is a non-ATPase component of the 26S proteasome regulatory particle, contributing to ATP-dependent degradation of ubiquitinated proteins and maintenance of protein homeostasis 1. The gene is structurally linked to SIRT3 in a bidirectional configuration with shared regulatory mechanisms, and both genes show associations with aging processes 1. PSMD13 expression is critical for cellular stress resistance and differentiation; IL-4 signaling suppresses PSMD13 expression in hematopoietic stem cells, impairing their stress tolerance and megakaryocytic differentiation capacity 2. In disease contexts, PSMD13 dysfunction has emerged as clinically significant. Genetic variants affecting PSMD13 alternative splicing (rs7128029) increase endometrial cancer susceptibility and correlate with poor survival outcomes 3. PSMD13 is upregulated in hepatocellular carcinoma where it promotes tumor proliferation, migration, and associates with M2 macrophage infiltration and immune checkpoint expression 4. Conversely, PSMD13 expression is markedly reduced in vitiligo skin lesions and blood, where it may influence disease progression via Nod-like receptor signaling 5. Additionally, PSMD13 genetic variants influence treatment-resistant depression susceptibility through altered proteasomal protein degradation capacity 6. PSMD13 also negatively regulates mutant RPE65 proteins in retinal degeneration through ubiquitination-mediated degradation 7. These findings establish PSMD13 as a multifunctional proteasomal component with broad relevance to aging, cancer, immune dysfunction, and neuropsychiatric disease.