Rearranged during transfection proto-oncogene receptor (RET)

The Rearranged during transfection proto-oncogene receptor (RET) is a receptor tyrosine kinase critical for the development and maintenance of several tissues, particularly in the nervous and excretory systems. RET is activated by binding members of the glial cell line-derived neurotrophic factor (GDNF) family, together with GFRα coreceptors[2][1]. Upon ligand binding, RET dimerizes, autophosphorylates, and triggers key downstream signaling pathways such as Ras/MAPK and PI3K/AKT, modulating cell proliferation, survival, and differentiation[3]. Mutations in RET can lead to oncogenic activation (gain-of-function), responsible for medullary thyroid cancer, multiple endocrine neoplasia type 2 (MEN2), and other cancers[2][1]. Loss-of-function mutations are causative in Hirschsprung's disease and certain neurodevelopmental disorders. Drugs targeting RET, such as selpercatinib and pralsetinib, inhibit aberrant RET signaling in cancers characterized by RET mutations or gene fusions. RET is associated with a unique extracellular domain structure compared to other receptor tyrosine kinases, featuring four cadherin-like domains and a cysteine-rich region, and exists in multiple isoforms through alternative splicing[1][2].

Other names

RETRet receptorProto-oncogene c-RetRearranged during transfectionRET proto-oncogene receptor tyrosine kinase

Inhibition of tyrosine kinase activity, Blockade of downstream signaling pathways (Ras/MAPK, PI3K/AKT), Inhibition of cell proliferation and survival