Artemin is a member of the Glia Cell-Derived Neurotrophic factor (GDNF) family ligands, which include GDNF, Persephin, Artemin, and Neurturin. GDNF family ligands are distant members of the Transforming Growth Factor beta (TGF-beta ) superfamily (1-4). Similar to other TGF-beta family proteins, Artemin is synthesized as a large precursor protein that is cleaved at the dibasic cleavage site (RXXR) to release the carboxy-terminal domain. The carboxy-terminal domain of Artemin contains the characteristic seven conserved cysteine residues necessary for the formation of the cysteine-knot and the single interchain disulfide bond. Biologically active Artemin is a disulfide-linked homodimer of the carboxy-terminal 113 amino acid residues. Mature mouse Artemin shares 88.5% amino acid sequence similarity with human Artemin. Mature Artemin also shares approximately 40% amino acid sequence identity with the other three members of the GDNF family ligands (5). Bioactivities of all GDNF family ligands are mediated through a receptor complex composed of a high affinity ligand binding component (GFR alpha -1-GFR alpha -4) and a common signaling component, cRET (receptor tyrosine kinase) (5-8). Artemin prefers to bind to GFR alpha -3 and activites the GFR alpha -3-RET. However, in the presence of RET, it can bind to GFR alpha -1 as well (4, 5, 9). Artemin has been shown to promote the survival and growth of various peripheral and central neurons, including sympathetic and dopaminergic neurons. It may also play an important role in the development of sympathetic neurons and several organs (5, 10, 11).