Collectively, these results emphasize the potential for overexpressed β-gal to be retained in the ER of GM1 gangliosidosis patient cells following lentivirus-mediated GLB1 gene therapy, where accumulation of precursor, nonlysosomal rhβ-gal can activate the unfolded protein response and trigger ER stress. This evidence concerns the gene GAL and GM1 gangliosidosis.