RET (ret proto-oncogene) is a member of the cadherin superfamily and a receptor tyrosine kinase, which are cell-surface molecules that transduce signals for cell growth and differentiation. It can undergo oncogenic activation in vivo and in vitro by cytogenetic rearrangement. Ligands that bind the Ret receptor include the glial cell line-derived neurotropic factor (GDNF) and its congeners neurturin, persephin and artemin. Alterations in the corresponding Ret gene are associated with diseases including papillary thyroid carcinoma, multiple endocrine neoplasia (type 2A and 2B), familial medullary thyroid carcinoma and a congenital developmental disorder known as Hirschsprung disease. The Tyr905 residue located in the Ret kinase domain plays a crucial role in Ret catalytic and biological activity. Substitution of Phe for Tyr905 dramatically inhibits Ret autophosphorylation activity.