Accumulated HS disrupts the lysosomal multienzyme complex of NEU1 with cathepsin A, β-galactosidase (GLB1), and glucosamine-6-sulfate sulfatase (GALNS), leading to NEU1 deficiency and partial GLB1 and GALNS deficiencies in cortical tissues and induced pluripotent stem cell–derived (iPSC-derived) cortical neurons of patients with neurological MPS. Here, NEU1 is linked to mucopolysaccharidosis.