Anti-ICAM NPs bearing acid sphingomyelinase (ASM), α-galactosidase (α-Gal), or α-glucosidase, the enzymes deficient in types A and B Niemann–Pick disease, Fabry disease, and Pompe disease, respectively, have shown enhanced enzyme delivery using various cellular models of the blood–brain barrier, neural cells, skeletal muscle cells, and endothelial cells, as well as both to brain and peripheral organs in vivo [29,30,31,32,33,34,35,36,37,38]. Here, SMPD1 is linked to Fabry disease.