Table 3.

Lysosome Storage Disorders (LSDs).

Sphingolipidoses
Enzymes	Role	Disease Name	Upregulated Cancers	Downregulated Cancers
β-Glucocerebrosidase (β-glucosidase) encoded by GBA	Breaks down glucocerebroside into glucose and ceramide.	Gaucher Disease (GD), also known as Glucocerebrosidase deficiency		GBA in liver (85).
α-Galactosidase A	Breaks down globotriaosylceramide (known as Gb3 or CD77)	Fabry disease, also known as Alpha-galactosidase A deficiency	Gb3 in breast (86, 87), ovarian (88), and colon cancer (89).
Acid ceramidase	Metabolizes ceramides into sphingosine and a fatty acid	Farber disease, also known as Farber lipogranulomatosis or Acid ceramidase deficiency	Prostate cancer (90, 91), head and neck squamous cell carcinoma (92), liver (93), and breast (94).
Acid sphingomyelinase (ASM)	Metabolizes the hydrolysis of sphingomyelin into phosphorylcholine and ceramide.	Niemann-Pick Disease Types A and B (NPD-A and B), also known as Sphingomyelinase deficiency		Breast, lung, thyroid, and bladder (95).
Glycoproteinoses
Enzymes	Role	Disease Name	Upregulated Cancers	Downregulated Cancers
Lysosomal α-mannosidase, encoded by MAN2B1	Breaks down oligosaccharides containing a mannose.	α-mannosidosis, also known as Alpha-mannosidase deficiency or Mannosidosis	MAN2B1 in bladder urothelial carcinoma, breast invasive carcinoma, colon adenocarcinoma, glioblastoma multiforme, low-grade gliomas, and laryngeal cancer (96, 97).
α-L-fucosidase, encoded by FUCA1	Cleaves fucose-rich oligosaccharides, glycoproteins, and glycolipids.	Fucosidosis, also known as Alpha-fucosidase deficiency	FUCA1 in glioblastoma multiforme (98), papillary thyroid cancer (PTCs) samples (99), and breast cancer (100).	FUCA1 in colorectal cancer (101), HCC (102), and anaplastic thyroid cancer (ATCs) samples (99).
Lysosomal neuraminidase-1 (NEU1; also known as sialidase)	Removes terminal sialic acid residues from sialo-rich oligosaccharides, glycoproteins and glycolipids.	Sialidosis, also known as Mucolipidosis Type I	HCC (103, 104), ovarian (105), and colon (106).
Mucopolysaccharidoses
Enzymes	Role	Disease Name	Upregulated Cancers	Downregulated Cancers
Alpha-L-iduronidase (IDUA)	Breaks down glycosaminoglycans, such as dermatan sulfate and heparan sulfate.	MPS I, also known as IDUA deficiency, Hurler syndrome, Scheie syndrome or Hurler-Scheie syndrome		Breast (107) and ovarian (108).
Iduronate-2-sulfatase (IDS)	Breaks down glycosaminoglycans, such as dermatan sulfate and heparan sulfate.	MPS II, also known as Hunter Syndrome or Iduronate 2-sulfatase deficiency		Breast (109).
Arylsulfatase B (ARSB; also known as N−acetylgalactosamine−4−sulfatase)	Breaks down glycosaminoglycans, such as dermatan sulfate and chondroitin sulfate.	MPS VI, also known as Maroteaux-Lamy syndrome or Arylsulfatase B deficiency		Melanoma (110), colorectal (111), prostate, and breast (112, 113).
β−glucuronidase, encoded by GUSB	Breaks down glycosaminoglycans, such as dermatan sulfate and keratan sulfate.	MPS VII, also known as Sly syndrome or Beta-glucuronidase deficiency	Colorectal (114), gastric (115), and pancreas (116). GUSB in HCC (117).