SIRT6 is a NAD+-dependent histone deacetylase that serves as a critical regulator of aging, inflammation, and metabolic homeostasis 1. The protein primarily functions through deacetylation of specific histone residues, particularly H3K9, H3K18, and H3K56, which modulates gene expression and chr19 structure 23. SIRT6 exhibits protective effects against cellular senescence by maintaining DNA repair pathways, preserving telomere integrity, and reducing oxidative stress-induced damage 4. The protein regulates multiple disease-relevant pathways: it attenuates osteoarthritis progression by deacetylating STAT5 and inhibiting IL-15/JAK3/STAT5 signaling 5, protects against vascular calcification by suppressing Runx2-mediated osteogenic transdifferentiation 6, and prevents age-related cataracts by regulating ferroptosis through SIRT6/p-Nrf2/GPX4 pathways 7. In inflammatory diseases, SIRT6 controls macrophage efferocytosis and inflammation resolution in diabetic periodontitis 8 and governs IL-17A pathogenicity in severe asthma by deacetylating RORγt 3. Additionally, SIRT6 protects against podocyte injury and proteinuria by epigenetically suppressing Notch signaling 2. These diverse functions establish SIRT6 as a promising therapeutic target for aging-related diseases, inflammatory conditions, and metabolic disorders.