Abstract

Dysmyelination contributes to several human diseases including multiple sclerosis, Charcot-Marie-Tooth, leukodystrophies, and schizophrenia and can result in serious neurological disability. Properly formed, compacted myelin sheaths are required for appropriate nerve conduction velocities and the health and survival of neurons. Many different molecular mechanisms contribute to dysmyelination and many of these mechanisms originate at the level of the endoplasmic reticulum. The endoplasmic reticulum is a critical organelle for myelin biosynthesis and maintenance as the site of myelin protein folding quality control, Ca²⁺ homeostasis, cholesterol biosynthesis, and modulation of cellular stress. This review paper highlights the role of the endoplasmic reticulum and its resident molecules as an upstream and dynamic contributor to myelin and myelin pathologies.