Myrf, short for Myelin Regulator Factor, is a master regulator governing myelin formation and maintenance in the central nervous system [2]. It is an unconventional transmembrane transcription factor that undergoes proteolytic self-processing for transcriptional regulation. Myrf is conserved across metazoans and has broad tissue expression, suggesting functions beyond myelination [2].

Microglia-derived exosomes can transfer miR-615-5p to oligodendrocyte precursor cells (OPCs), where miR-615-5p binds to MYRF and inhibits OPC maturation, thus modulating myelin regeneration. Targeting the miR-615-5p/MYRF axis could be a new therapy for demyelinating diseases [1]. In Myrfmut/+ mice, there are elevated intraocular pressure, fewer ganglion cells, and a thinner retinal nerve fiber layer, along with down-regulation of Dnmt3a, suggesting MYRF mutations are associated with primary angle-closure glaucoma [4]. Nanophthalmos-associated MYRF mutation in mice makes the eyes more susceptible to inflammation, which can be relieved by dexamethasone treatment [5]. Heterozygous loss-of-function variants in MYRF in humans can lead to abnormal development of the heart, genitourinary tract, diaphragm, and lungs, with phenotypes including congenital heart defects, genitourinary anomalies, congenital diaphragmatic hernia, and pulmonary hypoplasia [3]. MYRF haploinsufficiency also causes 46,XY and 46,XX disorders of sex development, with clinical symptoms like hypoplasia of Müllerian derivatives and ovaries in 46,XX DSD patients, and defective development of Sertoli and Leydig cells in 46,XY DSD patients [6].

In conclusion, Myrf plays crucial roles in myelin formation, and its mutations are associated with various diseases such as demyelinating diseases, primary angle-closure glaucoma, intraocular inflammation, and disorders of sex development. Studies on Myrf-related KO or mutant mouse models have provided valuable insights into these disease mechanisms, facilitating a better understanding of the gene's functions and potential therapeutic targets.