Ras moves to stay in place

• The amount of Ras at the plasma membrane (PM) determines whether and how Ras signals.
• Ras continuously leaks from the PM into the vast endomembrane system.
• Energy-consuming cyclic processes counter Ras leakage from the PM.
• Pharmacological interference with spatial cycles affects oncogenic Ras signaling.

Ras is a major intracellular signaling hub. This elevated position comes at a precarious cost: a single point mutation can cause aberrant signaling. The capacity of Ras for signaling is inextricably linked to its enrichment at the plasma membrane (PM). This PM localization is dynamically maintained by three essential elements: alteration of membrane affinities via lipidation and membrane-interaction motifs; trapping on specific membranes coupled with unidirectional vesicular transport to the PM; and regulation of diffusion via interaction with a solubilization factor. This system constitutes a cycle that primarily corrects for the entropic equilibration of Ras to all membranes that dilutes its signaling capacity. We illuminate how this reaction–diffusion system maintains an out-of-equilibrium localization of Ras GTPases and thereby confers signaling functionality to the PM.