In-frame insertion/deletion mutations and single base changes in JM domain (666 and 691) have been reported to cause gain-of-function, constitutively active, monomeric RET in familial and sporadic medullary thyroid cancer.21,52,53 With the loss of extracellular ligand-binding domain, transmembrane domain, and partial loss of the auto-inhibitory juxtamembrane domain, ΔRET is hypothesized to be active by auto-phosphorylation in a cytosolic and ligand-independent manner. The gene discussed is RET; the disease is medullary thyroid gland carcinoma.