Glial cell line-derived neurotrophic factor family receptor alpha 4 (GFRα4)

Glial cell line-derived neurotrophic factor family receptor alpha 4 (GFRα4) is a glycosylphosphatidylinositol (GPI)-anchored cell surface co-receptor predominantly expressed in the thyroid gland in humans[5]. It specifically binds persephin (PSPN), one of the glial cell line-derived neurotrophic factor (GDNF) family ligands, enabling activation of the RET receptor tyrosine kinase[5][8]. Upon ligand binding, GFRα4 forms part of a tripartite complex (ligand–GFRα4–RET) that triggers intracellular pathways driving differentiation, growth, and survival in neuronal and non-neuronal tissues[1][5][8]. Aberrant activation or expression of GFRα4 can contribute to oncogenesis, particularly in certain thyroid malignancies, making it of interest as a therapeutic target, though clinical agents directly targeting GFRα4 are not yet available[3][5].

Other names

GDNF family receptor alpha-4GFRA4

Typically, the pathway involves ligand (persephin, PSPN) binding to GFRα4, which triggers activation of the RET receptor tyrosine kinase and intracellular signaling cascades[1][5][8].