Collectively, our gene therapy studies in GM1 gangliosidosis patient cells are in agreement with Martin et al. (18), suggesting that GLB1 overexpression coincides with dose-dependent (Fig. 8 and Fig. S4) and time-dependent (Fig. S5) increases in early ER markers (PDI) and late ER markers (Grp78) of the unfolded protein response, as well as CHOP translocation, an indicator of prolonged ER stress. This evidence concerns the gene HSPA5 and GM1 gangliosidosis.