Despite the accumulation of aggregated proteins in the ER, we found that PD patient-derived midbrain cultures failed to upregulate XBP1, a transcription factor that is controlled by the inositol-requiring enzyme 1-α (IRE1α) branch of the UPR and upregulates chaperones GRP78 and GRP94 during proteomic stress20. Here, ERN1 is linked to Parkinson disease.