Neurotrophic factors includes neurokines, neurotrophins, and glial-cell-line derived neurotrophic factor (GDNF) ligands (GFLs). The GDNF family of ligands is comprised of artemin (ARTN), neurturin (NTN), and persephin (PSPN). They have similar functions in supporting specific neuronal populations in the central nervous system and basal forebrain with a NGF-comparable efficacy on both cholinergic and non-cholinergic neurons. They also support regulation of the maturation of the central nervous system as well as sympathetic, sensory and enteric neurons. GDNF was identified as a growth factor that supports survival of the embryonic dopaminergic neurons of midbrain and spinal motor neurons. They bind to the GDNF receptor alpha 1-4 (GFRα-1 to -4) and induce signaling through receptor tyrosine kinase RET activation. Persephin is not involved in supporting the peripheral nervous system. Binding of persephin to cell surface GFRα receptor triggers the dimerization of receptor RET and induces the autophosphorylation of the tyrosine kinase. Although persephin is a member of GFLs, studies indicate that treatment of fibroblasts presenting RET, coreceptor GFRα-1 or GFRα-2 double transfectants with Persephin does not induce a cellular response, which suggests a unique path of Persphin signaling through the help of other cofactors.