GAL and GM1 gangliosidosis: Our results suggest that the biophysical properties of β-gal, along with the therapeutic modality, should be considered when developing an effective treatment for GM1 gangliosidosis and that intermittent ICV-ERT dosing is a tunable therapeutic option that can safely and precisely deliver rhβ-gal to lysosomes to clear pathological lysosomal substrates and reverse neuropathology associated with the disease.