proteolipidprotein

Proteolipid protein (PLP) refers to the major integral membrane protein of central nervous system myelin. It is encoded by the PLP1 gene, located on the X chromosome, and exists mainly as two isoforms: the 30 kilodalton PLP protein and the alternative-spliced 22 kilodalton DM20. Both forms are produced in oligodendrocytes and are the most abundant proteins in CNS myelin, making up a substantial portion of its protein content.

Structurally, PLP/DM20 is a highly hydrophobic tetraspan membrane protein with four transmembrane helices. Its N- and C- termini are predicted to face the cytoplasm, while certain loops orient toward the extracellular side of the myelin membrane. The protein associates with cholesterol- and sphingolipid-rich membrane domains and is thought to contribute to the lateral organization and stability of the myelin sheath, particularly during membrane compaction.

Functionally, PLP and DM20 are essential for the proper formation and maintenance of CNS myelin. They participate in the compaction of myelin membranes and work in concert with other myelin proteins such as myelin basic protein (MBP) to establish the intraperiod and major dense lines that characterize compact myelin. PLP is also involved in lipid homeostasis within the myelin membrane and may participate in signaling pathways relevant to oligodendrocyte function.

Genetically, mutations or duplications of the PLP1 gene cause X-linked myelin disorders. Duplications or overexpression can lead to Pelizaeus–Merzbacher disease (PMD), a hypomyelinating leukodystrophy, whereas point mutations can produce a spectrum including PMD and spastic paraplegia type 2 (SPG2).