Does lysosomal rupture evoke Ca²⁺ release? A question of pores and stores

Lysosomotropic agents have been used to permeabilize lysosomes and thereby implicate these organelles in diverse cellular processes. Since lysosomes are Ca²⁺ stores, this rupturing action, particularly that induced by GPN, has also been used to rapidly release Ca²⁺ from lysosomes. However, a recent study has questioned the mechanism of action of GPN and concluded that, acutely, it does not permeabilize lysosomes but releases Ca²⁺ directly from the ER instead. We therefore appraise these provocative findings in the context of the existing literature. We suggest that further work is required to unequivocally rule out lysosomes as contributors to GPN-evoked Ca²⁺ signals.