EIF2AK4 and early-onset autosomal dominant Alzheimer disease: For example, recent work showed that pharmacologic activation of the ISR kinase GCN2 reduced mitochondrial fragmentation and respiratory chain dysfunction in cells deficient in the ISR kinase PERK18 – a condition linked to many neurodegenerative diseases including Alzheimer’s disease and Progressive Supranuclear Palsy.61,62 Further, the potential to pharmacologically access adaptive mitochondrial remodeling induced by ISR activation could allow correction of mitochondrial dysfunction induced by genetic, environmental, or aging-related insults.