GUSB

β-Glucuronidase (GUSB), also known as GUS or β-G, is a lysosomal hydrolase encoded by the GUSB gene. It catalyzes the hydrolysis of β-glucuronic acid residues from glycosaminoglycans (GAGs), including dermatan sulfate and heparan sulfate, facilitating their stepwise degradation. This enzyme operates within the lysosomal GAG catabolic pathway, critical for maintaining extracellular matrix homeostasis. Deficiencies in GUSB cause mucopolysaccharidosis type VII (MPS VII, Sly syndrome), a rare autosomal recessive disorder characterized by progressive accumulation of undegraded GAGs, leading to hepatosplenomegaly, skeletal dysplasia, and cognitive impairment. Current therapies include enzyme replacement therapy (ERT) with vestronidase alfa (Mepsevii™), approved in 2017, which alleviates somatic symptoms but cannot cross the blood-brain barrier. Investigational approaches, such as gene therapy using AAV vectors to deliver functional GUSB to the CNS, are under clinical evaluation (NCT04251065). Substrate reduction therapies and pharmacological chaperones remain exploratory for MPS VII.