Factors regulating lysosomal membrane permeabilization. This schematic presents a number of factors that may be responsible for lysosomal membrane permeabilization (LMP). The relative importance of each mechanism likely depends on the cell type and death stimulus. Mechanisms that are believed to safeguard lysosomal integrity and protect from lysosome-mediated cell death are also shown. “Changes in membrane lipid composition” includes membrane destabilizing factors such as phospholipase A2 and sphingosine, as well as LPM protective substances e.g., cholesterol and sphingomyelin. Abbreviations: JNK, c-Jun N-terminal kinase; LAPF, lysosome-associated apoptosis-inducing protein containing the pleckstrin homology and FYVE domains; Hsp, heat shock protein; ROS, reactive oxygen species; ANT, adenine nucleotide translocator; Ahr, aryl hydrocarbon receptor; LEDGF, lens epithelium-derived growth factor; LAMP, lysosome-associated membrane protein