MEN2A cysteine pathogenic variants constitutively activate RET through ligand-independent dimerisation7,12, whereas M918T, present in MEN2B patients, results in a conformational change that enables activation of both the dimer and monomer RET molecules, with RET activation and downstream signalling occurring even prior to exiting the endoplasmic reticulum7,12,13. This evidence concerns the gene RET and multiple endocrine neoplasia type 2B.