IDUA and mucopolysaccharidosis type 1: In the case of a lysosomal enzyme, such as iduronidase (IDUA), the enzyme mutated in Mucopolysaccharidosis Type I (MPSI), the enzyme was fused to the carboxyl terminus of the HC of the HIRMAb (Boado et al., 2008b), and this HIRMAb-IDUA fusion protein crosses the BBB via RMT on the endothelial IR and then undergoes receptor-mediated endocytosis into brain cells via the IR expressed on the neuronal cell membrane, followed by triage to the lysosomal compartment (Figure 4).