Gusb, encoding β -glucuronidase (GUS), is an enzyme essential for the degradation of glycosaminoglycans (GAGs) like heparan sulfate, dermatan sulfate, and chondroitin-4,6-sulfate [3]. Deficiency in Gusb leads to mucopolysaccharidosis VII (MPS VII; Sly syndrome), an autosomal recessive disorder with various symptoms including mental retardation, short stature, and hepatosplenomegaly due to the accumulation of undegraded GAGs in lysosomes [3].

In a canine MPS VII model, the transfer of GUSB using a helper-dependent canine adenovirus vector corrected neuropathology in the brain and improved corneal pathology [4,5]. In endometriosis, gut dysbiosis-derived GUSB promoted the development of the disease by affecting endometrial stromal cell proliferation and macrophage function [1]. In hepatocellular carcinoma, over-expression of GUSB led to primary resistance to anti-PD1 therapy by downregulating PD-L1 expression [2].

In conclusion, Gusb is crucial for GAG degradation, and its deficiency causes MPS VII. Studies using animal models, especially the canine MPS VII model, have shown potential for gene therapy in treating MPS VII-related neurological and corneal defects. Additionally, Gusb has been implicated in the development of endometriosis and resistance to anti-PD1 therapy in hepatocellular carcinoma, highlighting its significance in understanding and potentially treating these diseases.