Choreographing endo-lysosomal Ca²⁺ throughout the life of a phagosome

The emergence of endo-lysosomes as ubiquitous Ca²⁺ stores with their unique cohort of channels has resulted in their being implicated in a growing number of processes in an ever-increasing number of cell types. The architectural and regulatory constraints of these acidic Ca²⁺ stores distinguishes them from other larger Ca²⁺ sources such as the ER and influx across the plasma membrane. In view of recent advances in the understanding of the modes of operation, we discuss phagocytosis as a template for how endo-lysosomal Ca²⁺ signals (generated via TPC and TRPML channels) can be integrated in multiple sophisticated ways into biological processes. Phagocytosis illustrates how different endo-lysosomal Ca²⁺ signals drive different phases of a process, and how these can be altered by disease or infection.