Eukaryotic translation initiation factor 2 alpha kinase 3 encoded by EIF2AK3 phosphorylates the alpha subunit of eukaryotic translation-initiation factor 2, leading to its inactivation, and thus to a rapid reduction of translational initiation and repression of global protein synthesis. Eukaryotic translation initiation factor 2 alpha kinase 3 is thought to modulate mitochondrial function. It is a type I membrane protein located in the endoplasmic reticulum (ER), where it is induced by ER stress caused by malfolded proteins. Mutations in EIF2AK3 are associated with Wolcott-Rallison syndrome.