Myelin protein zero (MPZ) (MPZ)

Myelin protein zero (MPZ), also known as P0, is the primary structural protein of the peripheral nervous system (PNS) myelin, accounting for over 50% of the total protein content (UniProt P25189). It is a single-pass transmembrane glycoprotein belonging to the immunoglobulin superfamily that functions as a homophilic cell adhesion molecule, essentially acting as a molecular glue to hold the myelin layers together (NCBI Gene ID: 4359). The Large myelin protein zero (L-MPZ) is a specific isoform produced via translational read-through, adding a unique C-terminal extension that may play specialized roles in myelin stability (PMID: 27551077). Mutations in the MPZ gene are a major cause of hereditary neuropathies, including Charcot-Marie-Tooth disease type 1B (CMT1B) and Dejerine-Sottas syndrome, often resulting from protein misfolding and subsequent endoplasmic reticulum stress (OMIM 159440). While no small-molecule drugs are currently approved to target MPZ directly, it is a significant focus for gene therapy, antisense oligonucleotides, and pharmacological chaperones like Sephin1 aimed at reducing proteotoxicity in myelinating Schwann cells (PMID: 30104470).

Other names

P0L-MPZLarge myelin protein zeroMyelin peripheral proteinCHMCMT1BHMSN1B

Pharmacological chaperone activity and modulation of the integrated stress response to alleviate endoplasmic reticulum stress caused by misfolded proteins.