Rheb (RasÊhomologÊenriched inÊbrain) is a small GTPase that functions as an important mediator between the tumor suppressor proteins TSC1. Rheb shares about 30Ð40% sequence identity with members of the Ras/Rap subfamily of small GTPases. Human Rheb consists of 184 amino acid residues. The 169 N-terminal residues form the GTPase domain; the 15 C-terminal residues are hypervariable with a flexible structure and comprise a conserved carboxyl CAAXÊmotif that plays important roles in the farnesylation of Rheb and its association with membrane (1).