PMP22 is a peripheral myelin protein essential for proper myelination and myelin maintenance in the peripheral nervous system. 1 It is primarily expressed in compact myelin of peripheral nerves and functions in establishing proper myelin thickness, likely in response to axonal signals. 2 Recent evidence suggests PMP22 plays roles in Schwann cell cholesterol homeostasis, with disease-causing mutations disrupting cholesterol localization and trafficking necessary for healthy myelin formation. 3 PMP22 expression is tightly dosage-sensitive; alterations in PMP22 levels cause >50% of inherited peripheral neuropathies. 1 Gene duplication (chromosome 17.2) causes CMT1A through PMP22 overexpression, resulting in early hypermyelination. 2 Point mutations produce more severe phenotypes with hypomyelination and onion bulb formation, disturbing myelin formation and maintenance. 2 PMP22 deletion reduces gene expression, causing hereditary neuropathy with liability to pressure palsies (HNPP), suggesting PMP22 functions in myelin lamellae adhesion to prevent longitudinal sliding. 2 Clinically, PMP22 mutations cause CMT1A (60-70% of CMT cases), CMT1E, Dejerine-Sottas syndrome, and HNPP. 4 HNPP presents with recurrent focal neuropathies triggered by mechanical forces. 5 Current treatment remains symptomatic, though PMP22-targeted small interfering RNA and antisense oligonucleotides show promising therapeutic potential. 4