GUSB encodes glucuronidase beta, a lysosomal enzyme essential for degrading glycosaminoglycans (GAGs) including heparan sulfate, dermatan sulfate, and chondroitin sulfate 1. The enzyme plays a primary role in GAG catabolism, which is critical for normal connective tissue homeostasis 1. Deficiency of GUSB causes mucopolysaccharidosis VII (Sly syndrome), an autosomal recessive lysosomal storage disorder characterized by GAG accumulation in lysosomes, leading to mental retardation, short stature, hepatosplenomegaly, bone dysplasia, and hydrops fetalis 1. Over 49 unique disease-causing mutations have been identified in the GUSB gene, with significant genotype-phenotype correlation 1. Recently, elevated GUSB expression derived from dysbiotic gut microbiota has been implicated in endometriosis pathogenesis, promoting endometrial stromal cell proliferation and M2 macrophage transition 2. Emerging evidence suggests GUSB haploinsufficiency may represent a genetic risk factor for Alzheimer's disease; heterozygous loss-of-function mutations in GUSB increase amyloid-beta plaque formation in transgenic mouse models 3. GUSB is included among 25 genes recommended by 85% or more of rare disease experts for newborn screening via genome sequencing 4, reflecting its clinical significance in treatable metabolic disorders.