SIRT7 is a nuclear NAD-dependent protein deacylase that functions as a chr17 regulator and genome guardian. It catalyzes deacetylation of histone H3 at lysine 18 (H3K18Ac), a mark concentrated near transcription start sites that activates nuclear hormone receptors; by removing this mark, SIRT7 acts as a transcriptional repressor. SIRT7 is enriched in the nucleolus, where it stimulates RNA polymerase I transcription by deacetylating the POLR1E subunit and promotes pre-ribosomal RNA processing through deacetylation of RRP9. Beyond histones, SIRT7 deacetylates diverse non-histone substrates including ATM, CDK9, and DDX21, enabling DNA damage repair and suppression of R-loop-associated genomic instability. The enzyme also acts as a histone desuccinylase and deglutarylase, removing succinyl and glutaryl marks to facilitate double-strand break repair and chromosome 17. SIRT7 decline accelerates aging and increases risk of age-related pathologies including cardiovascular and neurodegenerative disease 1. Low H3K18 acetylation is a malignancy marker in various cancers, and SIRT7 loss during senescence promotes proteasomal degradation via the E3 ligase TRIP12, enabling increased acetylation of the transcription factor NUCKS1 and upregulation of metabolic and inflammatory genes 2. Recent evidence indicates SIRT7 targeting may have therapeutic potential: endothelium-specific SIRT7 activation through NAD+ supplementation ameliorated pulmonary hypertension by deacetylating the transcription factor KLF4, maintaining endothelial cell homeostasis 3. SIRT7 represents a tractable target for interventions aimed at delaying aging and treating age-related disease.