Four GDNF ligands (GDNF, neurturin, artemin and persephin), and mesencephalic astrocyte-derived neurotrophic factor (MANF) and conserved dopamine neurotrophic factor (CDNF) protect midbrain dopaminergic neurons that degenerate in Parkinson''s disease. Each GDNF ligand binds a specific coreceptor GDNF family receptor ? (GFR?), leading to the formation of a heterotetramer complex, which then interacts with receptor tyrosine kinase RET, the signalling receptor. The present work describes the structural and biochemical characterization of the GDNF-GFR?1 complex and the MANF and CDNF proteins.