Phenylalanine--tRNA ligase alpha subunit

FARSA encodes phenylalanine–tRNA ligase alpha subunit, a component of the aminoacyl-tRNA synthetase complex responsible for charging tRNA with phenylalanine during protein translation (UniProt: Q9Y285). The protein functions in the core translational machinery and is present across multiple cellular compartments. Beyond its housekeeping role, FARSA mutations cause Rajab interstitial lung disease with brain calcifications 2 (RILDBC2; MIM 619013), an autosomal recessive disorder marked by interstitial lung disease, growth delay, hypotonia, liver dysfunction, and diffuse brain calcifications.

In Alzheimer's disease, FARSA protein is significantly downregulated in post-mortem AD brain tissue relative to age-matched controls (mean log2 fold-change −1.041; Chaparral AD proteomics). This reduction was detected across a subcellular fractionation study using TMT-labeled quantitative proteomics of four fractions. The functional consequence of reduced FARSA in AD pathology remains to be clarified, though decreased aminoacyl-tRNA synthetase activity could potentially affect protein synthesis fidelity during neurodegeneration.