Certain GCase mutants (eg, N370S, L444P) have been reported to be retained in the endoplasmic reticulum (ER), triggering the unfolded protein response (UPR) and undergoing ER-associated degradation (ERAD) via the proteasome.24–26 We measured 3 markers of the UPR: splicing of the transcription factor Xbp1, increased transcription of C/EBP homologous protein (CHOP), and increased protein levels of the chaperone binding immunoglobulin protein (BiP).25 CHOP mRNA levels were increased in the putamen of PD+GBA (163%) and sporadic PD brains (189%; p < 0.05; see Fig 3D). The gene discussed is DDIT3; the disease is Parkinson disease.