EIF2AK4 and neurodegenerative disease: For example, we previously showed that halofuginone-dependent GCN2 activation restored cellular ER stress sensitivity and mitochondrial electron transport chain activity in cells deficient in the alternative ISR kinase PERK (Perea et al., 2023a) – a model of neurodegenerative diseases associated with reduced PERK activity such as PSP and AD (Park et al., 2023; Yuan et al., 2018).