Glial cell line-derived neurotrophic factor (GDNF) is a member of the TGF-β superfamily and was first identified as a growth factor supporting the survival of embryonic midbrain neurons. GDNF has been shown to promote the development, differentiation, and survival of dopaminergic neurons by signaling through GDNF family receptor α-1 (GFRα1) and the coreceptor Ret receptor tyrosine kinase. Dysregulated expression of GDNF has been reported to be associated with several mental diseases, which include depression and schizophrenia. GDNF is considered as a promising therapeutic agent for the treatment of Parkinson's disease because it can protect dopaminergic neurons from neurotoxins and promotes neuron regeneration after injury. In addition to the functions in the nervous system, GDNF is also required for the differentiation of spermatogonia and kidney development. Upregulated expression of GDNF was observed in various cancer cell lines and correlates with malignant cancer progression, suggesting a role of GDNF in carcinogenesis.