The GDNF family ligands (GFLs) belong to the super family of the TGF-β. They belong to the group of cystine-knot protein and function as homodimers¹. This family includes glial cell line-derived neurotrophic factor (GDNF), artemin (ARTN), Neurturin (NRTN) and persephin (PSPN)².

These factors are heavily involved in the development and function of the nervous system (both central and peripheral). In particular GDNF has an important role outside the nervous system where it plays a role in kidney morphogenesis¹.

In general GFLs all signal through a signal through the receptor tyrosine kinase Ret. Their specificity is implemented by different GDNF family receptor a (GFRα), which act as co-receptors. These extracellular proteins are bound to the plasma membrane via a glycosyl phosphatidyl inositol (GPI) anchor. GFRα1-4 are responsible for the binding of GDNF, NRTN, ARTN, and PSPN respectively and the subsequent activation of Ret. Soluble forms of the receptor by the cleavage of a yet unknown phospholipase or protease can be detected^1,3. Also alternative spliced forms of the protein can lead to soluble forms of GFRα receptors³.

In respect to their important role in development, individual knockout of either gdnf, gfra1 or ret gives rise to lethal phenotypes².