ALKBH8 (alkB homolog 8) is a tRNA-modifying enzyme that catalyzes the methylation of wobble uridine residues at position 34 in the anticodon loop of specific tRNAs, including tRNA-selenocysteine, tRNA-arginine, and tRNA-glutamate 1. This methyltransferase activity is crucial for proper codon decoding during translation elongation, with ALKBH8 deficiency causing ribosome pausing at adenine-ending codons and impaired translation of mRNAs enriched with these codons 2. The enzyme plays a critical role in selenoprotein synthesis through modification of tRNA-selenocysteine, thereby regulating cellular redox homeostasis 34. ALKBH8 loss results in decreased selenoprotein levels, increased oxidative stress, and ectopic synapse formation in the nervous system 3. Pathogenic variants in ALKBH8 cause intellectual developmental disorder, autosomal recessive 71, characterized by global developmental delay, facial dysmorphisms, and psychiatric problems 5. The gene shows upregulation in colorectal cancer as a direct Wnt/β-catenin target, promoting tumor progression through codon-specific translation of oncogenes like KRAS 2. In bladder cancer, ALKBH8 contributes to cell survival by regulating NOX-1-dependent ROS signaling and inhibiting apoptosis 6. Therapeutically, antioxidant treatments can reverse ALKBH8-associated memory impairments, suggesting potential treatment strategies 3.