METTL23 encodes a methyltransferase that functions as both a histone modifier and transcriptional regulator essential for normal cognitive development. The protein exhibits histone H3 arginine 17 methyltransferase activity and serves as a transcriptional partner of GABPA, regulating gene expression including THPO and ATP5B 1. METTL23 demonstrates dual cellular localization in nucleus and cytoplasm, with overexpression increasing transcriptional activity at target promoters while knockdown decreases expression of key genes 1. The protein shows strong predicted function as an S-adenosyl-methionine (SAM)-dependent methyltransferase with association to heat shock proteins as putative substrates 2. Disease relevance is established through autosomal recessive intellectual disability (ID), where loss-of-function mutations cause mild nonsyndromic ID with developmental delays and dysmorphic features 234. Additionally, pathogenic variants are associated with autosomal dominant normal-tension glaucoma, affecting approximately 1% of cases through disruption of NF-κB signaling pathways 56. Clinical significance encompasses both neurodevelopmental disorders and optic nerve degeneration, highlighting METTL23's critical role in methylation processes necessary for intact neuronal function and brain development 2.