Rearranged during transfection kinase (RET)

Rearranged during transfection kinase (RET) is a single-pass transmembrane receptor tyrosine kinase encoded by the RET proto-oncogene on chromosome 10q11.2. It plays an essential role in the development and maturation of various tissues including those derived from the neural crest, kidneys, and male germ cells. The extracellular domain contains cadherin-like repeats and cysteine-rich regions; upon ligand binding—typically members of the glial cell line-derived neurotrophic factor family—RET dimerizes and activates its intracellular tyrosine kinase domain to trigger downstream signaling cascades involved in cell growth, differentiation, survival, or apoptosis. Aberrant activation of RET through point mutations or gene fusions leads to constitutive signaling that drives oncogenesis in several cancers such as papillary thyroid carcinoma and non-small cell lung cancer. Conversely, loss-of-function mutations are implicated in developmental disorders like Hirschsprung’s disease. Targeted therapies using selective small-molecule inhibitors such as selpercatinib or pralsetinib have been developed for cancers driven by abnormal RET activity. RET is also notable as a dependence receptor: it can induce apoptosis when unbound by ligand but promotes survival when activated appropriately. Its clinical significance has made it both a diagnostic biomarker for certain malignancies with characteristic rearrangements/mutations as well as an important therapeutic target for precision oncology approaches[1][2][3][4][5].

Other names

RETRET proto-oncogeneRearranged during transfection receptor tyrosine kinaseREarranged during Transfection (RET) protein

Inhibition of aberrant RET kinase activity by selective small-molecule inhibitors to block downstream pro-survival and proliferative signaling pathways in cancer cells[1]