PUS10 is a dual-function pseudouridine synthase with distinct roles depending on subcellular localization 1. In the cytoplasm, PUS10 catalyzes pseudouridylation of tRNA, converting uracil residues at positions 54 and 55 to pseudouridine (Ψ54 and Ψ55) in the ψ GC loop of select tRNAs 2. This tRNA pseudouridylate synthase activity is enhanced by 1-methyladenosine at positions 53-61 of tRNAs 2. Notably, PUS10 lacks this enzymatic activity in the nucleus 1. In the nucleus, PUS10 promotes primary miRNA (pri-miRNA) processing through direct binding to pri-miRNAs and interaction with the DROSHA-DGCR8 microprocessor complex, independent of its catalytic activity 1. PUS10 also modulates apoptosis: during TRAIL-induced cell death, it translocates from the nucleus to mitochondria via CRM1-mediated export, reciprocally amplifying caspase-3 activity and promoting intrinsic mitochondrial cell death 3. Clinically, PUS10 variants are associated with shared genetic risk for inflammatory bowel disease, Crohn's disease, and celiac disease 4. Recently, PUS10-induced tRNA fragmentation was shown to regulate retrotransposon-driven inflammation through altered interferon signaling 5, establishing PUS10 as a viral mimicry modulator relevant to autoimmunity.