Pigment epithelium-derived factor (PEDF) was first identified as a 50kD secreted protein in conditioned medium from cultured fetal human retinal pigment epithelium (RPE) cells. More recently, PEDF was shown to have neurotrophic activity in the retina in vivo. PEDF is also a neurotrophic and neuroprotective factor in other systems, including cultured cerebellar granule cells, primary hippocampal neurons, spinal cord motor neurons and amphibian photoreceptors cultured in the absence of RPE cells. The binding of PEDF to retinoblastoma and cerebellar granule cells may be receptor-mediated. PEDF has been shown to be a potent inhibitor of angiogenesis in endothelial cell cultures and in rat cornea and retina in vivo.