Neurotrophic factors are a broad set of peptide growth factors that tightly regulate many critical aspects of the ontogeny of neurons, such as the number of neurons in a given population, neurite branching and synaptogenesis, adult synaptic plasticity and maturation of electrophysiological properties. Neurotrophic factors include neurotrophins, neurokines and GDNF family ligands. The GDNF family, consisting of GDNF, NRTN, ARTN and PSPN are distant members of the TGF-β superfamily that maintain several neuronal populations in the CNS, including midbrain dopamine neurons. In addition, GDNF, NRTN and ARTN support the survival and regulate the differentiation of many peripheral neurons, including sympathetic, parasympathetic, sensory and enteric neurons.Unlike other members of the TGF-β superfamily which signal through receptor serine-threonine kinases, the cellular responses to GDNF family ligands are mediated by a multi-component receptor complex consisting of Ret (an RTK) and a family of GPI-linked ligand-binding subunits known as GFR-α...