Tyrosine--tRNA ligase, cytoplasmic

YARS1 (tyrosine–tRNA ligase, cytoplasmic) is an aminoacyl-tRNA synthetase that catalyzes attachment of tyrosine to tRNA(Tyr) during protein synthesis (UniProt: P54577). Beyond its canonical tRNA ligase activity, YARS1 functions as a nuclear regulator of poly-ADP-ribosylation, particularly stimulating PARP1 activity when relocalized to the nucleus following resveratrol binding.

YARS1 is expressed in multiple tissues and has established associations with neurological disease. UniProt documents mutations causing Charcot-Marie-Tooth disease (dominant intermediate C) and infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD2), reflecting its importance in nervous system function and development.

Regarding Alzheimer's disease, YARS1 shows ambiguous regulation across brain subcellular fractions in post-mortem AD tissue compared to age-matched controls (Chaparral AD proteomics). The mean log2 fold-change across measured fractions is −0.0272, indicating minimal net change. This modest and inconsistent directionality suggests YARS1 is not substantially dysregulated in AD brain at the protein level, though further fraction-specific analysis may reveal localization-dependent changes relevant to disease pathology.