Phenylalanine--tRNA ligase beta subunit

Phenylalanine–tRNA ligase beta subunit (FARSB) is the regulatory component of phenylalanyl-tRNA synthetase, an aminoacyl-tRNA ligase essential for protein synthesis (UniProt: Q9NSD9). The enzyme catalyzes the attachment of phenylalanine to its cognate tRNA, a fundamental step in translation. FARSB mutations are associated with Rajab interstitial lung disease with brain calcifications 1 (RILDBC1), an autosomal recessive neurodevelopmental disorder presenting with developmental delay, hypotonia, and brain abnormalities including periventricular white matter changes and basal ganglia echogenicity.

In Alzheimer's Disease proteomics, FARSB shows an ambiguous direction of change across subcellular fractions in human post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics). The mean log2 fold-change is −0.31, suggesting a modest overall decrease, though the signal is inconsistent across the four measured fractions (P2, P3, S2, S3) in the TMT-labeled tandem mass spectrometry experiment. This modest and variable change warrants further investigation to determine whether altered protein synthesis capacity is relevant to AD pathogenesis.