The c-RET proto-oncogene, which was originally identified as a transforming gene by transfection of T-cell lymphoma DNA into NIH3T3 cells, is a member of the receptor tyrosine kinase (RTK) gene superfamily that encodes a receptor tyrosine kinase involved in the regulation of glial cell line-derived neurotrophic factor (GDNF) signaling. Signaling proteins, such as Grb7/Grb10, PLCγ, Shc/Enigma and Grb2, are recruited by activated c-RET protein through binding to the phosphorylated tyrosine residues in c-RET protein’s COOH-terminal sequence, Y905, Y1015, Y1062 and Y1096 respectively.  Moreover, results of in vivo studies suggest mutations of c-RET have been implicated in tumorigenesis, in which c-RET mRNA and/or protein have been found in tumors of neuroectodermal origin as well as in human neuroblastoma cell lines.