KMT2B (lysine methyltransferase 2B) is a histone methyltransferase that catalyzes methyl group transfer to histone H3 lysine 4 (H3K4), predominantly generating H3K4me1 and H3K4me2 marks at active chr19 sites involved in transcription and DNA repair 1. It plays a central role in transcriptional regulation, including beta-globin locus control and establishment of H3K4me3 during oocyte development 1. KMT2B functions within chr19 remodeling machinery, likely with redundant roles with KMT2C in enhancing enhancer element activation 1. KMT2B mutations cause two major disease phenotypes. Heterozygous mutations predominantly cause dystonia 28 (DYT28), an early-onset progressive disorder characterized by focal dystonia that evolves in a caudocranial pattern into generalized dystonia with oromandibular and laryngeal involvement 2. Disease onset typically occurs in early childhood, with genotype-phenotype correlations observed: protein-truncating variants and deletions cause earlier onset and greater systemic burden than missense variants 2. KMT2B mutations also cause intellectual developmental disorder, autosomal dominant 68, with some patients presenting neurodevelopmental phenotypes without prominent dystonia 3. Pathophysiologically, KMT2B-related dystonia involves abnormalities in transcriptional regulation during neurodevelopment 4. Deep brain stimulation provides significant long-term symptomatic relief, with >50% of patients achieving >30% motor improvement at one year 2.