Lysosomal beta-galactosidase (GLB1)

Human lysosomal beta-galactosidase (GLB1) is a vital acid hydrolase enzyme located within the lysosome, where it facilitates the degradation of GM1 gangliosides, keratan sulfate, and various glycoproteins by cleaving terminal beta-galactosyl residues (UniProt P16278; NCBI Gene 2720). Mutations in the GLB1 gene lead to a deficiency in this enzyme's activity, resulting in the toxic accumulation of substrates and the manifestation of lysosomal storage disorders, specifically GM1 gangliosidosis and Morquio syndrome type B (Mucopolysaccharidosis type IVB) (PMID: 31513940). GM1 gangliosidosis is characterized by progressive neurodegeneration and skeletal dysplasia, whereas Morquio syndrome type B primarily involves systemic skeletal abnormalities without significant central nervous system involvement (PMID: 31513940). Therapeutic interventions targeting GLB1 include pharmacological chaperones that stabilize misfolded mutant enzymes to enhance their residual activity, as well as enzyme replacement and gene therapies aimed at restoring functional enzyme levels (PMID: 27519484). A significant challenge in treating the neurological forms of GLB1 deficiency is the effective delivery of therapeutic agents across the blood-brain barrier (PMID: 31513940).

Other names

Beta-galactosidase 1Acid beta-galactosidaseGLB1Lactase (lysosomal)

Pharmacological chaperoning to stabilize mutant enzyme, enzyme replacement therapy to restore catalytic function, or gene therapy to induce endogenous expression.