Tryptophan--tRNA ligase, cytoplasmic

WARS1 (tryptophan–tRNA ligase, cytoplasmic) catalyzes the aminoacylation of tRNA(Trp) by adenylating tryptophan and transferring it to the tRNA acceptor end, a critical step in protein synthesis (UniProt: P23381). The protein also possesses angiostatic activity independent of its aminoacylation function, regulating endothelial cell responses through ERK, Akt, and eNOS signaling pathways. Mutations in WARS1 are associated with autosomal dominant distal hereditary motor neuronopathy 9 (HMND9) and autosomal recessive neurodevelopmental disorder with microcephaly and speech delay (UniProt: P23381).

WARS1 is downregulated in Alzheimer's disease brain tissue. Chaparral AD proteomics data from post-mortem AD brain compared to age-matched controls showed reduced WARS1 abundance with a mean log2 fold-change of −0.38 (Chaparral AD proteomics). This reduction was detected across subcellular fractions in a TMT-labeled mass spectrometry experiment, suggesting altered protein synthesis capacity or translational regulation in AD pathology.