Decoding extracellular matrix–lysosome cross-talk and its implications for neurodegenerative diseases

Lysosomes are versatile organelles that play pivotal roles in cellular recycling and signal transduction. They are crucial for the autophagic degradation and recycling of macromolecules, which facilitates the efficient turnover of cellular components. Beyond their intracellular roles, lysosomes also regulate the degradation and assembly of extracellular matrix (ECM) constituents, affecting ECM remodeling and the processing of signaling molecules essential for cellular communication and adaptation to the microenvironment. Conversely, the ECM regulates key lysosomal functions, including biogenesis, acidification, and subcellular positioning. In this Review, we discuss the bidirectional interaction between lysosomes and the ECM and explore its implications in the development and treatment of neurodegenerative disease.