Endolysosomal proteases and their inhibitors in immunity

The cellular endolysosomal compartment is dynamic, complex and incompletely understood. Its organelles and constituents vary between different cell types, but endolysosomal proteases are key components of this compartment in all cells. In immune cells, these proteases function in pathogen recognition and elimination, signal processing and cell homeostasis, and they are regulated by dedicated inhibitors. Pathogens can produce analogous proteases to subvert the host immune response. The balance in activity between a protease and its inhibitor can tune the immune response or cause damage as a result of mislocalized proteolysis. In this Review, we highlight recent developments in this area and emphasize the importance of studying the role of endolysosomal proteases, and their natural inhibitors, in the initiation and regulation of immune responses.