During α-synucleinopathy, prolonged ER stress occurs when the UPR cascade fails to restore ER homeostasis and ER stress cannot be alleviated; therefore, over activation of UPR diverts toward the apoptotic pathway, as PERK upregulates the expression of pro-apoptotic C/EBP homologous protein (CHOP) to mediate the ER stress-stimulated apoptotic pathways [6,19]. The gene discussed is DDIT3; the disease is synucleinopathy.