IDS (iduronate 2-sulfatase) is a lysosomal enzyme that catalyzes the degradation of glycosaminoglycans (GAGs), specifically dermatan sulfate and heparan sulfate 1. The enzyme functions within the lysosomal lumen and requires calcium ion binding for its activity. IDS is encoded by an X-linked gene containing 9 coding exons, with the human gene showing high conservation across vertebrates (60-99% sequence identity) 2. Deficiency in IDS activity due to genetic mutations causes mucopolysaccharidosis type II (MPS II or Hunter syndrome), an X-linked recessive lysosomal storage disorder 1. In MPS II patients, GAG accumulation occurs in most cells across all tissues and organs, resulting in severe somatic and neurological disorders 1. The IDS gene exhibits significant genetic heterogeneity, with over 779 point variants identified, including missense mutations (most common), large deletions-insertions, and complex rearrangements involving recombination with the pseudogene IDSP1 3. Approximately 22.5% of IDS mutations are de novo 4. Current enzyme replacement therapy with human IDS is limited by its inability to cross the blood-brain barrier, necessitating development of novel therapeutic approaches like BBB-penetrating fusion proteins for treating CNS manifestations 1.