GTPases (singular GTPase) are a large family of hydrolase enzymes that can bind and hydrolyze guanosine triphosphate (GTP). The GTP binding and hydrolysis takes place in the highly conserved G domain common to all GTPases.

GTPases play an important role in:

The hydrolysis of the γ phosphate of GTP into guanosine diphosphate (GDP) and P_i, inorganic phosphate, occurs by the S_N2 mechanism (see nucleophilic substitution) via a pentavalent intermediate state and is dependent on the magnesium ion Mg²⁺.

In most GTPases, the specificity for the base guanine is imparted by the base-recognition motif, which has the consensus sequence [N/T]KXD.

Regulatory GTPases, also called the GTPase superfamily, are GTPases used for regulation of other biochemical processes. Most prominent among the regulatory GTPases are the G proteins.

All regulatory GTPases have a common mechanism that enables them to switch a signal transduction chain on and off. Toggling the switch is performed by the unidirectional change of the GTPase from the active, GTP-bound form to the inactive, GDP-bound form by hydrolysis of the GTP through intrinsic GTPase-activity, effectively switching the GTPase off. This reaction is initiated by GTPase-activating proteins (GAPs), coming from another signal transduction pathway. It can be reverted (switching the GTPase on again) by Guanine nucleotide exchange factors (GEFs), which cause the GDP to dissociate from the GTPase, leading to its association with a new GTP. This closes the cycle to the active state of the GTPase; the irreversible hydrolysis of the GTP to GDP forces the cycle to run only in one direction. Only the active state of the GTPase can transduce a signal to a reaction chain.

Randy W. Schekman (born December 30, 1948) is an American cell biologist at the University of California, Berkeley and former Editor-in-Chief of Proceedings of the National Academy of Sciences. In 2011 he was announced as the editor of eLife a new high profile open access journal published by the Howard Hughes Medical Institute, the Max Planck Society and the Wellcome Trust launching in 2012. He was elected to the National Academy of Sciences in 1992.

In 2002, Schekman received the Albert Lasker Award for Basic Medical Research and Louisa Gross Horwitz Prize of Columbia University along with James Rothman for their discovery of cellular membrane trafficking, a process that cells use to organize their activities and communicate with their environment.

The Schekman laboratory carries out research into molecular descriptions of the process of membrane assembly and vesicular traffic in eukaryotic cells including yeast.