Glial cell line-derived neurotrophic factor (GDNF) is a potent survival factor for central and peripheral neurons and is essential for the development of kidneys and the enteric nerves system. Physiological responses to GDNF require the presence of a novel glycosylphosphadidylinositol linked protein GDNFRα, which is a cell surface receptor for GDNF. The cDNA encoding GDNFRα from human, rat, chicken and mouse have been cloned recently. GDNFRα was also termed Ret ligand 1 (RETL1) or TGF-β-related neurotrophic factor receptor 1 (TrnR1) and nominated as GFRα-1 recently. GFRα-1 binds GDNF specifically and mediates activation of the Ret protein tyrosine kinase (PTK). Thus, GDNF, GFRα and the Ret PTK from a complex to transduce GDNF signal and to mediate GDNF function.