Peripheral Myelin Protein-22 and Its Prominence in Charcot-Marie-Tooth Disease

allele, resulting in a common and usually mild form of CMT, hereditary neuropathy with liability to pressure palsies (HNPP). The rare type 1E CMT (CMT1E) is caused by amino acid variations in PMP22. The most common form of CMT (CMT1A) is caused by a third wild type (WT) allele of PMP22. The disease mechanisms of CMT1A are still incompletely understood, but there is much evidence that a major driver is proteostasis stress caused by WT PMP22 overexpression upon induction of myelination in SCs, possibly compounded by gain-of-function effects. Here, we explore PMP22's structure, functions, trafficking, role in CMT, and prospects for successful therapeutic intervention.