Long known as digestive organelles, lysosomes have now emerged as multifaceted centers responsible for degradation, nutrient sensing, and immunity. Growing evidence also implicates role of lysosome-related mechanisms in pathologic process. In this review, we discuss physiological function of lysosomes and, more importantly, how the homeostasis of lysosomes is disrupted in several diseases, including
atherosclerosis,
neurodegenerative diseases, autoimmune disorders,
pancreatitis, lysosomal storage disorders, and malignant
tumors. In
atherosclerosis and
Gaucher disease, dysfunction of lysosomes changes
cytokine secretion from macrophages, partially through
inflammasome activation. In
neurodegenerative diseases, defect autophagy facilitates accumulation of toxic
protein and dysfunctional organelles leading to neuron death. Lysosomal dysfunction has been demonstrated in pathology of
pancreatitis. Abnormal autophagy activation or inhibition has been revealed in autoimmune disorders. In tumor microenvironment, malignant phenotypes, including
tumorigenesis, growth regulation, invasion, drug resistance, and
radiotherapy resistance, of
tumor cells and behaviors of tumor-associated macrophages, fibroblasts, dendritic cells, and T cells are also mediated by lysosomes. Based on these findings, a series of therapeutic methods targeting
lysosomal proteins and processes have been developed from bench to bedside. In a word, present researches corroborate lysosomes to be pivotal organelles for understanding pathology of
atherosclerosis,
neurodegenerative diseases, autoimmune disorders,
pancreatitis, and lysosomal storage disorders, and malignant
tumors and developing novel therapeutic strategies.