The Ret proto-oncogene is structurally related to the growing family of tyrosine kinase transmembrane receptors and is involved in GDNF signaling. By alternative splicing, two isoforms of the Ret proto-oncogene product are generated. The isoforms differ from each other by having either 9 or 51 carboxyterminal amino acids. The Ret gene products include two glycosylated proteins and, in Tunicamycin treated cells, a non-glycosylated protein consistent with the predicted Ret molecular weight based on sequence analysis. Tumorspecific rearrangements of the Ret proto-oncogene have been identified in papillary thyroid carcinomas leading to the formation of different transforming fusion proteins sharing the tyrosine kinase domain of Ret. In contrast to the Ret proto-oncogene, the rearranged forms are constitutively phosphorylated on tyrosine and are translocated from the membrane to the cytoplasm.