TYW3 is a probable S-adenosyl-L-methionine-dependent methyltransferase that functions as a component of the wybutosine biosynthesis pathway 1. Wybutosine is a hypermodified guanosine nucleoside found at the 3' position adjacent to the anticodon of eukaryotic phenylalanine tRNA, where it stabilizes codon-anticodon interactions during ribosomal decoding 1. TYW3 acts within a multi-component enzymatic complex with TYW2 and TYW4 to catalyze sequential reactions in wybutosine synthesis from precursor tRNA 1. Beyond its canonical tRNA modification role, TYW3 has emerged as a metabolic regulator with disease relevance. Genetic variants near TYW3/CRYZ are associated with circulating resistin levels, an inflammatory hormone linked to insulin resistance and cardiovascular disease risk 2. TYW3 promoter methylation changes during metabolic dysfunction-associated steatotic liver disease (MASLD) progression correlate inversely with gene expression and associate with hepatocellular carcinoma survival outcomes 3. Additionally, TYW3/CRYZ methylation patterns are associated with birth-weight discordance in twins, suggesting developmental programming effects on metabolic health 4. TYW3 has also been identified as a prognostic feature gene in hepatocellular carcinoma risk stratification 5, and DNA methylation near TYW3 shows suggestive association with tic spectrum disorder potentially through mTOR pathway involvement 6.