Consistent with the Knudson ‘two-hit’ tumor-suppressor gene model [9], a first germline mutation inactivating one allele of either TSC1 or TSC2, and subsequently a somatic event (often loss of heterozygosity) inactivating the second allele, result in upregulation of the mTOR pathway and lead to overactive cell growth and proliferation [10]. Here, TSC2 is linked to neoplasm.