Lysosomal beta-galactosidase (GLB1) (GLB1)

Lysosomal beta-galactosidase (GLB1) is a hydrolase enzyme essential for the catabolism of GM1 gangliosides, glycoproteins, and glycosaminoglycans such as keratan sulfate [6, 7]. Encoded by the GLB1 gene, it primarily functions within the lysosome to maintain cellular lipid and carbohydrate balance, particularly in the central nervous system and skeletal tissues [1, 8]. Mutations in GLB1 lead to two distinct autosomal recessive disorders: GM1 gangliosidosis, characterized by progressive neurodegeneration, and Morquio syndrome type B (MPS IVB), which involves severe skeletal abnormalities [4, 11]. An alternatively spliced isoform of the gene also produces an elastin-binding protein (S-Gal) that facilitates the assembly of elastic fibers in the extracellular matrix [10]. Therapeutic approaches targeting this pathway include gene therapies like PBGM01 and AXO-AAV-GM1, which aim to restore functional enzyme production [2, 5, 14]. Additionally, pharmacological chaperones such as NOEV are being investigated to stabilize misfolded mutant enzymes and enhance their residual activity [16, 19]. A major challenge in drug development for GLB1-related diseases is achieving sufficient therapeutic levels across the blood-brain barrier to halt neurological decline [18]. Monitoring of these therapies often relies on biomarkers such as beta-galactosidase activity in leukocytes and GM1 ganglioside levels in the cerebrospinal fluid [3, 12].

Other names

Beta-galactosidase 1Acid beta-galactosidaseGalactosidase beta 1S-GalElastin-binding proteinLactase (lysosomal)

Gene therapy (transgene expression to restore enzyme production), Pharmacological chaperone (stabilization of misfolded mutant enzymes to enhance residual activity), and Substrate reduction therapy (indirectly via inhibition of ganglioside synthesis)