HSPA5 and Alzheimer disease: Similarly, in ER stress pathways and unfolded protein response activation, genes coding for proteins in all three key axes—transcription factor XBP1, HSPA5 (GRP ortholog), and EIF2K3 (PERK ortholog), and transcription factor ATF6—are differentially upregulated in APOEε2/c AD samples; (d) a cellular pathway that recognizes unfolded/misfolded proteins in the ER and targets them for ubiquitination and subsequent degradation by the proteasome in the cytosol is called ERAD.