α-Synuclein has been shown to activate the UPR through several mechanisms: (1) Some studies showed that α-synuclein oligomers are responsible for the inhibition of the proteasome machinery, (2) α-synuclein aggregates were reported to interact directly with BiP and activate the UPR in PD, although it is unclear how they are translocated into the ER [56] and (3) α-synuclein interacts with RAB1 [70], impairing COPII vesicular trafficking, and therefore, inhibiting ATF6 activation and blocking this pro-adaptive branch of the UPR, leading to apoptosis [57]. The gene discussed is ATF6; the disease is Parkinson disease.