Table 1.

Diseases related with lysosomal dysfunction

Diseases	Lysosomal dysfunction	Outcomes	Reference
Atherosclerosis	Lysosomal acid lipase deficient	Substantial decrease in lysosomal acid lipase activity leads to premature atherosclerosis in human	[57]
	OxLDL or cholesterol crystal accumulation	OxLDL or cholesterol crystal causes lysosomal membrane permeability, autophagy deficient, mitochondrial dysfunction, inflammasome activation, and apoptosis	[54, 58, 61–63]
Neurodegeneration diseases
Alzheimer's disease	Presenilin 1 mutation	Defective Presenilin 1-dependent lysosomal acidification is one of the main causes of early-onset familial AD	[93–95, 340, 341]
	Becn1 ablation	Heterozygous deletion of beclin 1 (Becn1) results in autophagy disruption, Aβ deposition, and neurodegeneration	[97]
	Cathepsin D mutation	The T-allele of cathepsin D rs17571 increases risk of AD	[92]
	Cathepsin B ablation	Ablation of cathepsin B increases the abundance of Aβ42 and potentiates plaque deposition	[91]
Parkinson’s disease	Snca mutation	A53T point mutation in the Snca gene causes familial PD	[107, 108]
	Atp13a2 ablation	Atp13a2 depletion leads to lysosomal membrane instability, impaired acidification, blocked clearance of autophagosomes, α-syn accumulation, and cell death	[109, 110]
	Gba1 mutation	Mutations in the Gba1 gene are important risk factors for PD	[113]
Huntington disease	Htt mutation	Mutated HTT protein has abnormally long polyglutamine (polyQ) repeats near the N-terminus, which promotes formation of toxic oligomers and neuronal inclusion bodies	[119, 120]
	Wdfy3 ablation	Depletion of Wdfy3 accelerates the accumulation of polyQ aggregates	[127]
	Sqstm1 knockdown	Sqstm1 knockdown increases mHTT-induced cell death	[128]
Pancreatitis	Impaired autophagy flux	Increased autophagosome formation and decreased autophagosome clearance are observed	[140, 342]
	Imbalanced cathepsin B and cathepsin L	Imbalance between cathepsin B and cathepain L contributes to accumulation of activated intracellular trypsin	[140]
Autoimmune disorders
Systemic lupus erythematosus	Enhanced autophagy in T cells	Enhanced autophagy causes imbalanced T cell subsets	[146–148]
	Defect LC3-associated phagocytosis	Defect LC3-associated phagocytosis leads to blunted clearance of dying cells and elevated inflammation	[149]
	Defect lysosomal acidification	Macrophages in lupus shows elevated lysosomal pH	[343]
Crohn’s disease	Defect autophagy	Human or mice deficient in ATG16L1 are more susceptible to Crohn’s disease	[150, 151]
	Defect lysosomal acidification	Elevated luminal pH links lysosomal dysfunction with Crohn’s disease risk	[344]
Rheumatoid arthritis	Impaired autophagy	Reduced autophagy links altered metabolism and T cell exhaustion	[152]
Multiple sclerosis	Enhanced autophagy	Enhanced ATG5 expression in T cells is correlated with more sever disability	[153]
Lysosomal storage disorder
Niemann-Pick type C (NPC) disease	Npc1 or Npc2 mutation	Defective NPC1 or NPC2 causes lysosomal accumulation of cholesterol and glycosphingolipids leading to hepatic, pulmonary, and neuropsychiatric disorder	[345]
Fabry disease	Galactosidase α mutation	Galactosidase α mutation causes globotriaosylceramide accumulation in lysosomes leading to vascular diseases	[346]
Tay-Sachs disease	β-hexosaminidase α mutation	Deficient β-hexosaminidase α causes GM2 ganglioside accumulation in lysosomes of nerve cells leading to neuro disorder	[347]
Mucopolysaccharidoses diseases	Mutation in mucopolysaccharide catabolic enzymes	Lysosomal accumulation of mucopolysaccharides leads to disorders in bone, cartilage, connective tissues, and nervous	[348]
Pompe disease	α glucosidase mutation	Mutated α glucosidase causes glycogen accumulation in lysosomes leading to cardiac and respiratory failure	[349]
Gaucher disease	glucosylceramidase β mutation	Glucosylceramide accumulates in macrophage lysosomes leading to disorder in visceral organs and nervous system	[162]