FARSB (phenylalanyl-tRNA synthetase subunit beta) encodes a regulatory β-subunit of the tetrameric phenylalanyl-tRNA synthetase complex, which catalyzes the aminoacylation of phenylalanine-tRNA 1. This enzyme is essential for protein synthesis, as it ligates phenylalanine onto tRNA molecules in the cytoplasm 1. FARSB functions through protein heterotetramerization with FARSA α-subunits and localizes to multiple cellular compartments including cytoplasm, nucleoplasm, and membrane regions 1. Pathogenic biallelic variants in FARSB cause autosomal recessive aminoacyl-tRNA synthetase-related disease, characterized by severe multisystem developmental dysfunction with phenotypic overlap to other ARS-deficiency disorders 1. Loss-of-function FARSB mutations destabilize the entire phenylalanyl-tRNA synthetase complex, reducing both FARSB and FARSA protein levels 1. FARSB variants have been identified in patients with intellectual disability in consanguineous populations 2, and are associated with Rajab interstitial lung disease with brain calcifications 3. Beyond monogenic disease, FARSB is upregulated in hepatocellular carcinoma and serves as a prognostic biomarker; high FARSB expression promotes HCC progression via mTORC1 activation and ferroptosis inhibition 45. FARSB is also identified as a candidate peripheral biomarker for bipolar II disorder, correlating with cognitive performance deficits 67.