Lysosomal storage diseases (LSDs) (designated intractable disease 9) are congenital metabolic disorders that develop central and peripheral symptoms due to the excessive accumulation of substrates that should be metabolized in the lysosome in each organ and tissue, caused by the latent genetic mutation of lysosomal hydrolases and related factors, resulting in a deficiency of the enzyme activity. More than 50 types of LSDs are known, and fundamental treatments targeting the synthesis mechanism of responsible lysosomal enzymes and accumulated substrates have been clinically applied for several types of LSDs [1]. The treatments (Fig. 83.1) include enzyme replacement therapy (ERT) that delivers recombinant enzyme preparations from outside the cell to the lysosome using the endocytosis mechanism via binding of the N-glycans carrying terminal mannose 6-phosphate (M6P) or mannose (Man) residues, which are added specifically to the lysosomal enzyme, to the cation-independent M6P receptor (CI-M6PR) or Man receptor (ManR) on the surface of target tissue cells; hematopoietic stem cell transplantation (HSCT) that replaces normal enzymes secreted from donor cells by transplanting normal donor-derived hematopoietic stem cells; gene therapy (GT) based on the cross-correction effect of replacing normal enzymes secreted from introduced or transplanted cells to surrounding deficient cells by introducing therapeutic enzyme genes directly into patient tissues or using viral vectors; substrate reduction therapy (SRT) that suppresses the synthesis of accumulating substrates with substrate analogs; and pharmacological chaperone therapy (PCT) that promotes the transport of mutant enzymes that retain partial activity to the lysosome using substrate analog preparations that bind to mis-sense mutant enzymes that are synthesized in the endoplasmic reticulum and have partially abnormal folding.