CARS1 (cysteinyl-tRNA synthetase 1) catalyzes the ATP-dependent aminoacylation of cysteine to tRNA(Cys), a critical step in protein synthesis 1. The enzyme functions as a cytoplasmic aminoacyl-tRNA synthetase with established roles in translation initiation and elongation. Loss-of-function CARS1 variants cause a multisystem neurodevelopmental disorder characterized by microcephaly, developmental delay, brittle hair and nails, and variable additional manifestations 12. Disease severity correlates with variant functional impact; compound heterozygous mutations can produce hypomorphic or complete loss-of-function effects 1. The phenotypic spectrum has expanded to include hepatopathy, hypothyroidism, muscular hypotonia, ataxia, and congenital hyperinsulinism, indicating broader metabolic involvement 2. Beyond monogenic disease, CARS1 has emerging roles in complex disorders. A recurrent de novo missense variant (p.E712V) associates with sporadic moyamoya disease, exhibiting early-onset cerebrovascular stenosis in affected carriers 3. Additionally, CARS1 contains an endogenous TLR2/6 ligand domain with immunomodulatory properties capable of activating dendritic cells and enhancing anti-tumor immunity 4. CARS1 is also implicated as an autoantigen in antisynthetase syndrome and serves as a prognostic marker in mesothelioma 56.