eIF2-P activates the integrated stress response by inducing a conformational change in eIF2B that decreases substrate (eIF2) binding and reduces eIF2B's catalytic activity.

Genetically induced conformational modulation of eIF2B activates the Integrated Stress Response by impairing nucleotide exchange.

A drug-like molecule called ISRIB, which activates the translation initiation factor eIF2B, antagonizes stress responses as diverse as protein misfolding and nutrient deprivation, and restores protein synthesis, enhancing memory.

Neurological pathology and chronic activation of the induced stress response are caused by expression of a truncated EIF2B5 in vanishing white matter disease.

Phosphorylated translation initiation factor eIF2, a potent inhibitor of protein synthesis in eukaryotic cells, is also inhibitory to protein synthesis when bound to GTP and initiator tRNA broadening the reach and immediacy of eIF2-mediated control.

Vanishing White Matter Disease mutations compromise the function of the essential translation initiation factor eIF2B by destabilizing the holoenzyme, and the small molecule ISRIB reverses their pathogenic effect by promoting complex formation.

Eliminating eukaryotic initiation factor 2 (eIF2) from wild-type budding yeast had little impact on translation of individual mRNAs, including those with regulatory upstream open-reading frames, even when canonical initiation factor eIF2 activity was impaired.

The N-terminal domain (NTD) of the initiation factor eIF5 bound to the 40S subunit at the precise location vacated by eIF1 promotes tRNAi accommodation at AUG codons.

A compound that prevents stressors such as UV light and viral infection from downregulating protein synthesis inside cells improves memory performance in mice.

Boosting the function of translation factor eIF2B by chronic small molecule administration prevents pathology in a neurodegenerative model of Vanishing White Matter disease characterized by a maladaptive stress response.