SARS1 (seryl-tRNA synthetase 1) is a dual-function enzyme with critical roles in both translation and transcriptional regulation. Primarily, SARS1 catalyzes aminoacylation of tRNA(Ser) through a two-step reaction: serine activation by ATP to form Ser-AMP, followed by transfer to the acceptor end of tRNA(Ser) 1. SARS1 also aminoacylates tRNA(Sec) with serine, generating a precursor for selenocysteinyl-tRNA(Sec) synthesis 1. Beyond translation, SARS1 functions as a nuclear transcriptional regulator, binding the VEGFA promoter and preventing MYC-mediated transcriptional activation, thereby inhibiting angiogenesis 2. This nuclear-localized activity is modulated by post-translational modifications: phosphorylation diminishes VEGFA promoter binding under hypoxia, while glycosylation reduces nuclear localization under nutrient stress 2. Clinically, biallelic SARS1 variants cause autosomal recessive neurodevelopmental disorders characterized by microcephaly, developmental delay, intellectual disability, and brain anomalies 3. A de novo splice site deletion produces a loss-of-function dominant negative effect, inducing cellular senescence and growth arrest 1. Additionally, SARS1 is significantly overexpressed in head and neck squamous cell carcinoma, where it promotes tumor progression via PI3K-AKT pathway activation and correlates with poor prognosis 4. These pleiotropic functions establish SARS1 as both a disease-relevant therapeutic target and a cellular hub protein.