M6 is a membrane glycoprotein that is expressed on central neurons and certain polarized epithelia from early developmental stage. Antibodies against M6 interfere with cerebellar neurite outgrowth in vitro. Two closely related cDNAs were obtained by expression cloning, both of which showed high homology with the major CNS myelin protein PLP/DM20. Although M6 and PLP/DM20 share many molecular characteristics, in situ hybridization revealed nonoverlapping distributions of their mRNAs in mouse CNS. The identification of a gene family including neuron-specific M6 and glia-specific PLP/DM20 in CNS suggests a broader functional role for these molecules than myelination.