Proteolipid protein (PLP) is the most abundant protein of central nervous system (CNS) myelin. Because of its predicted topography, PLP has been assumed to function as a structural component of myelin, providing stability and maintaining the compact lamellar structure. However, developmental studies have shown that the PLP gene is active long before myelination begins. This and other evidence from various PLP mutants and transgenic models has fueled speculation that PLP or other products of the gene have additional, nonstructural roles both within and outside the CNS. PLP is structurally related to a family of ion channel proteins which includes the connexins, synaptophysins and various neurotransmitter receptors, and there is some experimental evidence which supports a role for PLP in ion gating. Other provocative ideas are that the PLP gene may influence autocrine signaling within oligodendrocytes or that PLP mRNAs have a function apart from protein coding.