TMEM63A, associated with hypomyelinating leukodystrophies, is an evolutionarily conserved regulator of myelination.

ABSTRACT: Infantile hypomyelinating leukodystrophy 19 (HLD19) is a rare genetic disorder where patients exhibit reduced myelin in central nervous system (CNS) white matter tracts and present with varied neurological symptoms. The causative gene TMEM63A encodes a mechanosensitive ion channel whose role in myelination is largely unexplored. Our study shows that TMEM63A is a major regulator of oligodendrocyte (OL)-dependent myelination in the CNS. In mouse and zebrafish, Tmem63a inactivation led to early deficits in myelination, recapitulating the HLD19 phenotype. OL-specific conditional mouse knockouts of Tmem63a exhibited transient reductions in myelin, indicating that TMEM63A regulates myelination cell-autonomously. We show that TMEM63A is present at the plasma membrane and on l

SUBMITTER: Halford J 

PROVIDER: S-EPMC12318207 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature