FTSJ1 is an X-linked RNA 2'-O-methyltransferase that catalyzes methylation of the 2'-O-ribose at positions 32 and 34 of the tRNA anticodon loop 12. Position 32 methylation requires the cofactor THADA, while position 34 methylation requires WDR6 12. FTSJ1 modifies at least 11 tRNA species including tRNAPhe, tRNALeu, and selenocysteine tRNA, with these modifications being essential for faithful cytoplasmic translation 23. Position 34 methylation specifically promotes efficient UUU codon translation 2. In melanoma, FTSJ1-mediated selenocysteine tRNA methylation enables efficient selenoprotein synthesis, protecting against oxidative stress and reducing metastatic potential 3. FTSJ1 is required for neurogenesis and normal neuron morphology; its loss causes long, thin spine neurites and memory deficits in both Drosophila and mammals 4. FTSJ1 mutations cause X-linked intellectual disability through impaired translation of genes supporting synaptic organization and nervous system function 5. Loss of FTSJ1 also promotes glycolysis in lung cancer by enhancing PGK1 translation, suggesting potential therapeutic targeting in non-small cell lung cancer 6. FTSJ1 dysfunction affects multiple organ systems beyond the brain, including bone metabolism, immune function, and pain sensation 7.