NENF is a secreted protein that is expressed in neurons but not glial cells of the brain. This protein has neurotrophic activity in primary cultured mouse neurons but not mitogenic activity in primary cultured mouse astrocytes. NENF activated mitogen-activated protein (MAP) and phosphotidylinositol-3 kinase pathways and could be inhibited by pertussis toxin but not receptor tyrosine kinases, suggesting that NENF acts through a Gi/Go-protein-coupled receptor.