Neurofibromatosis type 2 (NF2) is an autosomal dominant disease which predisposes primarily to CNS tumors such as schwannomas (vestibular and spinal), meningiomas, ependymomas and juvenile posterior lenticular opacities. Allelic losses on chromosome 22q first suggested the existence of a tumor suppressor on this autosome in accordance with Knudson's 'two hit' model. The gene was identified by positional cloning and found to encode a novel protein schwannomin (also known as merlin), with high sequence similarity to the band 4.1 family of proteins. This similarity suggested a new mechanism of tumor suppression since it was the first time a structural protein had been associated with a human tumor. Mutation analysis confirmed that inactivation of the NF2 gene occurred in NF2 tumors and a majority of sporadic schwannomas and meningiomas. Expression and functional studies have provided additional information on the possible involvement of this novel tumor suppressor in cell differentiation, embryogenesis and growth suppression.