Translation initiation factor eIF2B subunit delta

EIF2B4 (translation initiation factor eIF2B subunit delta) is a component of the eIF2B complex that catalyzes GDP-to-GTP exchange on eIF2-gamma, thereby regulating the availability of initiator methionyl-tRNA and controlling global translation rates (UniProt: Q9UI10). When eIF2-alpha is phosphorylated, eIF2B4 binding is repressed, which further suppresses translation initiation under stress conditions.

EIF2B4 is primarily expressed in the central nervous system and is associated with leukoencephalopathy with vanishing white matter 4 (VWM4, MIM 620314), a rare autosomal recessive neurodegenerative disorder characterized by progressive cerebellar ataxia, spasticity, and cognitive decline with white matter degeneration (UniProt: Q9UI10).

In Alzheimer's disease, EIF2B4 is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.30 (Chaparral AD proteomics). This reduction may impair translation initiation capacity in affected neurons, potentially contributing to protein synthesis deficits observed in AD pathology.