TRUB2 is a pseudouridine synthase that catalyzes the post-transcriptional isomerization of uridine to pseudouridine (Ψ) in mitochondrial RNAs. As a component of a functional protein-RNA module containing RCC1L, NGRN, RPUSD3, RPUSD4, FASTKD2, and 16S mitochondrial rRNA, TRUB2 regulates 16S mt-rRNA abundance and is essential for intra-mitochondrial translation and oxidative phosphorylation 1. TRUB2 catalyzes pseudouridylation of specific mitochondrial mRNAs, including COXI and COXIII 2, and produces pseudouridine-55 in mitochondrial tRNAs within the psi GC loop 3. Mechanistically, TRUB2 modifies specific residues in mitochondrial mRNAs that are critical for ribosomal assembly and protein synthesis; depletion of TRUB2 results in mitochondrial protein synthesis defects and oxidative phosphorylation assembly failures without affecting mRNA levels 2. While earlier studies suggested TRUB2 possessed enzymatic activity, recent comprehensive pseudouridine mapping revealed that TRUB2 does not exhibit noticeable enzymatic activity in human cells 4. TRUB2 is essential for cell viability, as knockout studies confirmed it as a core essential gene 2. Given its role in mitochondrial translation, TRUB2 dysfunction likely contributes to mitochondrial disorders and metabolic diseases.