NARS1 encodes asparaginyl-tRNA synthetase 1, a cytoplasmic enzyme that catalyzes the ATP-dependent attachment of asparagine to tRNA(Asn) in protein synthesis 1. The enzyme functions as a homodimer, with the dimerization interface being critical for catalytic activity and tRNA binding 2. Beyond its essential role in translation, NARS1 acts as a signaling molecule that can induce migration of CCR3-expressing cells and is required for proper proliferation of radial glial cells during cerebral cortex development 1. Pathogenic variants in NARS1 cause a spectrum of neurodevelopmental disorders with microcephaly, seizures, peripheral neuropathy, and ataxia 1. De novo heterozygous mutations can exert toxic gain-of-function effects, while biallelic mutations cause partial loss-of-function 1. Dominant variants demonstrate dominant-negative properties by forming defective heterodimers with wild-type subunits, thereby impairing overall enzymatic function 23. NARS1 is also associated with inherited peripheral neuropathies, including axonal Charcot-Marie-Tooth disease and distal hereditary motor neuropathy 45. The severity of dominant-negative effects correlates with clinical phenotype complexity, with variants causing both central and peripheral nervous system features showing more severe dominant-negative properties than those causing isolated peripheral neuropathy 3.