Neurotrophic factor that enhances survival and morphological differentiation of dopaminergic neurons and increases their high-affinity dopamine uptake. Homodimer; disulfide-linked (PubMed:8493557, PubMed:8988018, PubMed:19478429). Interacts with RET (PubMed:21994944). Interacts (via propeptide) with SORL1 (via N-terminal ectodomain); this interaction affects GDNF-regulated, but not constitutive secretion (PubMed:15364913, PubMed:21994944, PubMed:23333276). Also interacts with SORL1 in complex with GFRA1; this interaction leads to GDNF endocytosis and lysosomal degradation (PubMed:23333276). In the brain, predominantly expressed in the striatum with highest levels in the caudate and lowest in the putamen. Isoform 2 is absent from most tissues except for low levels in intestine and kidney. Highest expression of isoform 3 is found in pancreatic islets. Isoform 5 is expressed at very low levels in putamen, nucleus accumbens, prefrontal cortex, amygdala, hypothalamus and intestine. Isoform 3 is up-regulated in the middle temporal gyrus of Alzheimer disease patients while isoform 2 shows no change. By cAMP, 12-O-tetradecanoylphorbol-13-acetate (TPA) and FGF2. Disease susceptibility is associated with variants affecting the gene represented in this entry. The gene represented in this entry may act as a disease modifier. Belongs to the TGF-beta family. GDNF subfamily.