To become activated, GTPases must bind to GTP. Since mechanisms to convert bound GDP directly into GTP are unknown, the inactive GTPases are induced to release bound GDP by the action of distinct regulatory proteins called guanine nucleotide exchange factors or GEFs.[1][2] The nucleotide-free GTPase protein quickly rebinds GTP, which is in far excess in healthy cells over GDP, allowing the GTPase to enter the active conformation state and promote its effects on the cell.[2][3] For many GTPases, activation of GEFs is the primary control mechanism in the stimulation of the GTPase signaling functions, although GAPs also play an important role.