The ret proto-oncogene encodes a cell surface glycoprotein belonging to a member of the receptor tyrosinek inase family and is located on chromosome 10q11.2. Three main 3= splice isoforms have been characterised from papillary thyroid carcinomas,the selves originating from thyroid epithelial cells.ret expression is observed in several regions of the central nervous system; in the developing cranial nerve ganglia and a subset of cells within dorsal root ganglia, in motor neurons in the spinal cord and hindbrain, in neuroretina and the growing tips of the renal collecting ducts in developing kidney. Some patients with Hirschsprung=s disease have severe developmental abnormalitites of the kidney and these phenotypic abnormalities may be linked with  mutations of ret proto-oncogene.About 70 per cent of individuals who carry one of the documented ret  mutations that predispose to multiple endocrine neoplasia type II (MENII) will develop clinically significant thyroid C cell derived tumours in their lifetime.