GDNF family receptor alpha-like (GFRAL) is a ~43 kDa protein. Brainstem-restricted receptor for GDF15 hormone, which triggers an aversive response, characterized by nausea, vomiting, and/or loss of appetite in response to various stresses. The aversive response is both required to reduce continuing exposure to those stresses at the time of exposure and to promote avoidance behavior in the future. The GDF15-GFRAL aversive response is triggered by stresses, such as anticancer drugs (camptothecin or cisplatin), cancers or drugs such as metformin. Upon interaction with its ligand, GDF15, mediates the GDF15-induced autophosphorylation and activation of the RET tyrosine kinase receptor, leading to activation of MAPK- and AKT- signaling pathways. Ligand-binding activates GFRAL-expressing neurons localized in the area postrema and nucleus tractus solitarius of the brainstem. 1. Mullican, SE. et al. (2017) Nature medicine 23, 1150-1157. PMID: 288460972. Emmerson, PJ. et al. (2017) Nature medicine 23, 1215-1219. PMID: 288460983. Yang, L. et al. (2017) Nature medicine 23, 1158-1166. PMID: 288460995. Tsai, VW. et al. (2019) International journal of obesity (2005) 43, 2370-2380. PMID: 311521546. Borner, T. et al. (2020) Cell metabolism 31, 351-362.e5. PMID: 319288868. Sabatini, PV. et al. (2021) Proceedings of the National Academy of Sciences of the United States of America 118. PMID: 3359391610. Benichou, O. et al. (2023) Cell metabolism 35, 274-286.e10. PMID: 36630958 | 
