TYW5 is a tRNA hydroxylase that catalyzes the hydroxylation of 7-(α-amino-α-carboxypropyl)wyosine (yW-72) into undermodified hydroxywybutosine (OHyW*) as a component of the wybutosine biosynthesis pathway 1. The enzyme functions as a Fe(II)/2-oxoglutarate-dependent oxygenase containing a Jumonji C (JmjC) domain with a β-jellyroll catalytic fold and forms homodimers through C-terminal helix bundles for tRNA recognition 2. Wybutosine and its derivatives are hypermodified guanosines at position 37 of phenylalanine tRNA, essential for accurate codon translation 1. Beyond its canonical tRNA modification role, TYW5 has emerged as a significant schizophrenia risk gene. Genome-wide association studies combined with brain expression quantitative trait loci analyses identified TYW5 as associated with schizophrenia susceptibility 34. The schizophrenia risk variants rs796364 and rs281759 disrupt transcription factor binding and modulate TYW5 expression in the brain; increased TYW5 expression is observed in schizophrenia cases compared to controls 5. TYW5 overexpression alters neural stem cell proliferation and differentiation, as well as dendritic spine density, suggesting pathogenic mechanisms involving neurodevelopmental disruption 5. These findings identify TYW5 as a potential therapeutic target for schizophrenia.