Isoleucine--tRNA ligase, cytoplasmic

IARS1 (isoleucine–tRNA ligase, cytoplasmic) catalyzes the two-step aminoacylation of isoleucine-specific tRNA, a fundamental step in protein translation (UniProt: P41252). The protein is ubiquitously expressed and essential for cellular protein synthesis. Mutations in IARS1 cause growth retardation, impaired intellectual development, hypotonia, and hepatopathy (GRIDHH, MIM 617093), an autosomal recessive disorder, highlighting its critical role in metabolic function.

In Alzheimer's disease, IARS1 is consistently downregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.55 (Chaparral AD proteomics). This observation was derived from quantitative proteomics across subcellular fractions of human brain tissue. The downregulation of translational machinery components such as IARS1 may reflect broader disruptions in protein synthesis capacity in AD brains, potentially contributing to neuronal dysfunction and cell death.