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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 GDNFRalpha, which is a cell surface receptor for GDNF. The cDNAs encoding GDNFRalpha from human, rat, chicken and mouse have been cloned recently. GDNFRalpha was also termed Ret ligand 1 (RETL1) or TGF-beta-related neurotrophic factor receptor 1 (TrnR1) and nominated as GFRalpha-1 recently. GFRalpha-1 binds GDNF specifically and mediates activation of the Ret protein tyrosine kinase (PTK). Thus, GDNF, GFRalpha and the Ret PTK form a complex to transduce GDNF signal and to mediate GDNF function.