Transmembrane protein 63 (TMEM63A) is a mechanosensitive ion channel (MSC) that plays an important role in the process of myelination. TMEM63A was identified as the causative gene of hypomyelinating leukodystrophy 19 (HLD19) in 2019. Myelin is a structure formed by oligodendrocytes in the nervous system, which has both nutrient axons and accelerated action potential conduction. Myelin dysfunction can be manifested as hypomyelination, demyelination and myelin vacuolization. Myelin is rich in lipids, and different lipids are involved in important processes such as myelination, repairment and recognition of glial cells and axons. HLD19 caused by TMEM63A variants is a hypomyelinating disease. TMEM63A variants can cause changes in osmotic pressure, and TMEM63A transmembrane protein on cells can be mechanically stimulated to generate electric current, thus affecting oligodendrocyte differentiation and maturation, resulting in abnormal myelination. At the same time, TMEM63A variations can also cause abnormal distribution of cell membrane lipids, affecting the normal function of lipids. Abnormal lipids by participating in different myelination links eventually lead to myelination disorders.