The 2818 amino acid neurofibromin protein is involved in a variety of human diseases, including several sporadic cancers, as well as the common genetic disorder neurofibromatosis type I. Although the underlying mechanism of these diseases seems to involve defects in the GTPase-activating activity of neurofibromin, which regulates the RAS family of small GTPases and downstream mitogen-activated protein kinase pathways, this activity resides in a small portion of the protein. The gene discussed is NF1; the disease is cancer.