We determined that the neuroprotective potential of exogenous GRP78 is linked to its ability to (i) prevent the manifestation of α-syn pathology, (ii) block ER stress-dependent apoptosis, and (iii) mitigate the excessive activation of microglia by targeting NF-κB signaling pathways in the LC-induced rat model of preclinical PD. This evidence concerns the gene HSPA5 and Parkinson disease.