MYRF (myelin regulatory factor) is a master transcription factor essential for oligodendrocyte maturation and CNS myelination 1. It recognizes the DNA sequence 5'-CTGGYAC-3' in regulatory regions to directly activate myelin genes including MBP, MOG, MAG, and PLP1 [UniProt annotation]. Uniquely, MYRF is an unconventional transmembrane transcription factor that undergoes intramolecular chaperone-mediated trimerization and self-cleavage, allowing its N-terminal DNA-binding domain to translocate to the nucleus 1. Beyond myelination maintenance, MYRF is required for nutritional regulation of oligodendrocyte differentiation affecting perineuronal net remodeling 2 and for cognitive performance during working memory training 3. MYRF haploinsufficiency causes Cardiac-Urogenital Syndrome (CUGS), characterized by congenital heart defects, genitourinary anomalies, and ocular abnormalities 45. MYRF mutations also cause nanophthalmos with associated angle-closure glaucoma through interaction with DNMT3A affecting DNA methylation and retinal cell functions 6. Patients with MYRF variants show notably thin retinal nerve fiber layers 7. The broad tissue expression and developmental lethality upon complete loss indicate MYRF's multifaceted roles extending beyond myelination, though these mechanisms remain incompletely understood 1.