| Protein Name |
Peripheral Myelin Protein 22 |
| Gene |
PMP22 |
| UniProt |
P60265 |
| Molecular Weight |
~22 kDa |
| Subcellular Localization |
Myelin membrane, plasma membrane |
| Protein Family |
Tetraspanin family |
| Structure |
Four transmembrane domains |
Pmp22 Protein — Peripheral Myelin Protein 22 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
PMP22 (Peripheral Myelin Protein 22, also known as Myelin Protein 22) is a 22-kDa tetraspan membrane protein encoded by the PMP22 gene. It is a major component of the peripheral nervous system myelin sheath, comprising approximately 2-5% of total myelin protein. The protein is essential for normal peripheral nerve function and is implicated in Charcot-Marie-Tooth disease.
PMP22 is a small tetraspan membrane protein with the following structural features:
- Four transmembrane domains: Spanning the myelin membrane
- Two extracellular loops: Important for protein-protein interactions
- Intracellular N- and C-termini: Cytoplasmic domains involved in signaling
- Molecular weight: Approximately 22 kDa
- N-glycosylation sites: Post-translational modifications affect trafficking
The protein adopts a compact structure that integrates into the lipid bilayer, contributing to the formation of the intraperiod line of compact myelin.
¶ Myelin Formation and Maintenance
- Myelin Assembly: PMP22 is incorporated into the compact myelin sheath, where it helps maintain structural integrity
- Schwann Cell Function: Essential for proper Schwann cell differentiation and myelination
- Protein Trafficking: Involved in transport of other myelin proteins
- Myelin Stability: Maintains the integrity of the myelin sheath over time
PMP22 interacts with several proteins in the myelin sheath:
- Myelin Protein Zero (MPZ): Coordinated expression for proper myelination
- Peripheral Myelin Protein 2 (PMP2): Co-localization in myelin
- Integrins: Schwann cell adhesion and signaling
CMT1A is caused by duplication of the PMP22 gene region on chromosome 17p12, leading to:
- Overexpression: 50% increase in PMP22 protein levels
- Myelin Abnormalities: Hypermyelination, onion bulb formation
- Demyelination: Secondary axonal degeneration
- Clinical Features: Progressive distal weakness, sensory loss, foot deformities
HNPP results from PMP22 deletion (haploinsufficiency):
- Reduced PMP22: Insufficient protein for normal myelin
- Focal Myelin Thickening: Tomacula formation
- Pressure Sensitivity: Susceptibility to compression injuries
Severe PMP22 mutations can cause this early-onset severe neuropathy:
- Early Onset: Infancy or early childhood
- Profound Weakness: Severe motor and sensory deficits
- Marked Demyelination: Very slow nerve conduction velocities
ASO-based approaches to reduce PMP22 overexpression in CMT1A:
- Preclinical Results: Reduced PMP22 mRNA and protein in animal models
- Improved Myelin: Decreased demyelination and onion bulb formation
- Clinical Trials: Early-phase trials ongoing
- Gene Silencing: RNA interference to reduce PMP22 expression
- Gene Editing: CRISPR-based approaches to correct mutations
- Viral Vectors: AAV-mediated gene delivery
- Retinoids: Modulate PMP22 expression via RAR pathways
- HDAC Inhibitors: Epigenetic approaches to gene regulation
- The peripheral myelin protein 22 gene and Charcot-Marie-Tooth disease type 1A. Brain, 2017.
- PMP22: the magic widget of Charcot-Marie-Tooth disease. Trends in Neurosciences, 2019.
- ASO-based reduction of PMP22 attenuates demyelination and improves neuropathy phenotypes. Brain, 2019.
- Structure of the peripheral myelin protein 22. Journal of Molecular Biology, 2018.
- Charcot-Marie-Tooth disease and related disorders. Neurology, 2020.
The study of Pmp22 Protein — Peripheral Myelin Protein 22 has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- The peripheral myelin protein 22 gene and Charcot-Marie-Tooth disease type 1A. Brain, 2017. DOI
- PMP22: the magic widget of Charcot-Marie-Tooth disease. Trends in Neurosciences, 2019. DOI
- ASO-based reduction of PMP22 attenuates demyelination and improves neuropathy phenotypes. Brain, 2019. DOI
- Structure of the peripheral myelin protein 22. Journal of Molecular Biology, 2018. DOI
- Charcot-Marie-Tooth disease and related disorders. Neurology, 2020. DOI
- UniProt: P60265
Page auto-generated from NeuroWiki protein database. Last updated: 2026-03-05.