EPRS1 encodes glutamyl-prolyl-tRNA synthetase 1, a bifunctional aminoacyl-tRNA synthetase that catalyzes the attachment of glutamate and proline to their cognate tRNAs for protein synthesis 1. The enzyme exists within the cytoplasmic multi-tRNA synthetase complex (MSC) under normal conditions 2. Upon various stimuli, EPRS1 exhibits noncanonical functions through stimulus-dependent phosphorylation and complex dissociation 2. In immune responses, phosphorylated EPRS1 can form the GAIT complex to inhibit translation of inflammatory mRNAs 2. In cancer, AKT-dependent nuclear localization of EPRS1 activates PARP1, promoting DNA repair and tumor cell survival 1. EPRS1 also contributes to fibrosis through both translational and nontranslational pathways, promoting fibroblast activation and collagen production while causing mitochondrial dysfunction 34. The protein modulates immune cell activity, enhancing T cell proliferation during tubulointerstitial nephritis 5. Pathogenic variants in EPRS1 cause hypomyelinating leukodystrophy-15 through defects in mRNA processing and reduced protein expression 67. EPRS1 also interacts with SARS-CoV-2 RNA elements to enhance viral gene expression 8. These diverse functions position EPRS1 as a critical regulatory hub beyond its primary aminoacylation activity.