Mol Biol Rep. 2025 Sep 10. 52(1): 881
Lysosome-dependent cell death (LDCD) is a regulated form of cell death initiated by increased lysosomal membrane permeability, leading to the cytoplasmic release of lysosomal enzymes and subsequent cellular damage. Molecular mechanisms controlling LDCD include lysosomal membrane instability and lysosomal enzyme release, which together lead to cell damage. A more profound comprehension of these underlying mechanisms may reveal new therapeutic targets for diseases associated with lysosomal dysfunction. This crucial process is implicated in numerous pathological conditions, including neurodegenerative diseases, various types of cancer, cardiovascular disorders, and autoimmune diseases. Despite the considerable therapeutic implications of LDCD, recent years have witnessed a notable absence of comprehensive reviews addressing the exploration of LDCD-related therapeutic targets in disease management. This review systematically discusses the molecular pathways of LDCD, its role in disease pathogenesis, potential clinical biomarkers, and therapeutic interventions. This extensive endeavor aims to establish a robust foundation for researchers to explore the complexities of LDCD in greater depth and to propel drug discovery in this highly promising field.
Keywords: Cathepsins; Cell death pathways; Disease associations; Lysosomal membrane permeabilization; Lysosome-dependent cell death; Therapeutic target