Aminoacyl-tRNA synthetases (ARSs) function to transfer amino acids to cognate tRNA molecules, which are required for protein translation. VARS encodes the only known valine cytoplasmic-localized aminoacyl-tRNA synthetase which is essential during eukaryotic translation. VARS belongs to class-I aminoacyl-tRNA synthetase family and is located in the class III region of the major histocompatibility complex. VARS mutations lead to a neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy.