Eukaryotic translation initiation factor 2B subunit delta (EIF2B4)

Eukaryotic translation initiation factor 2B subunit delta (EIF2B4) is the delta subunit of the eIF2B complex, a critical guanine nucleotide exchange factor (GEF) required for initiation of eukaryotic protein synthesis. The eIF2B complex consists of five subunits (α, β, γ, δ, ε); the δ subunit, encoded by EIF2B4, helps regulate the catalytic and regulatory activities of the complex, particularly in response to stress signals. eIF2B catalyzes the exchange of GDP for GTP on the initiation factor eIF2, enabling the recycling of eIF2 and continued translation initiation. EIF2B4 is especially important in the integrated stress response by controlling protein synthesis rates when cells face environmental changes or pathological stresses. Mutations in EIF2B4 impair eIF2B function, causing susceptibility to disorders such as vanishing white matter disease, which primarily affects central nervous system myelin and may involve ovarian failure. There are currently no approved drugs directly targeting EIF2B4, but genetic mutations serve as biomarkers for patient selection and diagnosis of related leukodystrophies. Disruption of eIF2B/EIF2B4 is a notable safety concern due to its essential role in cellular proteostasis and neurological health.

Other names

Translation initiation factor eIF2B subunit deltaEIF2B4EIF2BDEIF2BdeltaEIF-2BDKFZp586J0119EIF2BeIF2B GDP-GTP exchange factor subunit deltaVWM4eukaryotic translation initiation factor 2B, subunit 4 (delta, 67kD)eukaryotic translation initiation factor 2B, subunit 4 delta, 67kDatranslation initiation factor eIF-2B subunit deltatranslation initiation factor eIF-2b delta subunit

Modulation of the integrated stress response via eIF2B activity (potential experimental/early-stage compounds)