TRMT2B is a mitochondrial S-adenosyl-L-methionine-dependent methyltransferase that catalyzes the formation of 5-methyl-uridine (m5U) in mitochondrial RNA species 1. Specifically, TRMT2B catalyzes methylation of uridine at position 54 (m5U54) in all mitochondrial tRNAs and methylates uridine at position 429 (m5U429) in 12S rRNA 1. Despite its enzymatic function, TRMT2B is not essential for cellular viability, with gene knockout showing no obvious effects on RNA stability, mitochondrial translation, or cellular growth 1. Clinically, TRMT2B variants have emerged as relevant to neurodegenerative disease. Missense and splicing variants in TRMT2B were identified in patients with juvenile amyotrophic lateral sclerosis (JALS), with functional studies revealing mitochondrial dysfunction including decreased mitochondria number, swollen mitochondria, reduced mitochondrial complex I activity, lower aerobic respiration, and elevated reactive oxygen species 2. Additionally, TRMT2B expression is altered in Alzheimer's disease, where it was identified as a downregulated gene potentially involved in neuroinflammatory pathways 3. TRMT2B also serves as one of six mitochondrial RNA modification-related genes in a prognostic signature for lower grade gliomas 4.