Ras GTPase-activating protein-binding protein 2

G3BP2 (Ras GTPase-activating protein-binding protein 2) is a 482-amino-acid scaffold protein that plays an essential role in cytoplasmic stress granule formation. It functions as a platform for antiviral signaling and promotes the assembly of stress granules—membraneless, phase-separated compartments that sequester stalled translation machinery and mRNAs in response to cellular stress (UniProt: Q9UN86). The protein triggers RNA-dependent liquid-liquid phase separation upon binding unfolded RNA, serving as a molecular switch responsive to elevated intracellular free RNA concentrations.

Stress granules are critical nodes in the cellular stress response pathway, allowing cells to rapidly suppress translation and redirect resources during adverse conditions. G3BP2's role in organizing these transient membraneless compartments makes it central to translational control and innate immune signaling networks (UniProt: Q9UN86).

G3BP2 is associated with Alzheimer's Disease and is downregulated in AD brain tissue. Chaparral AD proteomics analysis of human post-mortem AD brain compared to age-matched controls revealed a mean log2 fold-change of −0.45 across one subcellular fraction in TMT-labeled, data-dependent acquisition mass spectrometry (Chaparral AD proteomics). This downregulation suggests potential dysregulation of stress granule dynamics and translational control in the AD brain.