Glial cell line-derived neurotrophic factor (GDNF) and the related neurotrophic factor neurturin (NTN) are potent survival factors for central and peripheral neurons. GDNF is a glycosylated, disulfide-bonded homodimer that is distantly related to the TGFβ superfamily of growth factors. Three receptors for these factors, GFRα-1 (also designated GDNFR-α, RETL1 or TrnR-1), GFRα-2 (also designated GDNFR-β, RETL2, NTNR-α or TrnR-2) and GFRα-3 have been identified. The receptors do not contain transmembrane domains and are attached to the cell membrane by glycosyl-phosphoinositol linkage. Both GFRα-1 and GFRα-2 have been shown to mediate the GDNF-dependent and NTN-dependent phosphorylation and activation of the tyrosine kinase Ret. GFRα-3 is expressed only during development.