Two-pore and TRP cation channels in endolysosomal osmo-/mechanosensation and volume regulation.

Two pore channels (TPCs) and mucolipins (TRPML) are the most prominent cation channels expressed in endolysosomes. Recently, roles of TPCs and TRPML2 have been revealed in regulating and detecting osmotically-driven changes in the surface-to-volume ratio of endolysosomes to promote endocytic and recycling traffic. TPCs and TRPML2 are highly expressed in macrophages and contribute to immune cell function. Here, we provide an overview of the emerging roles of these channels in innate immune cells, in particular macrophages, and highlight two models for osmo-mechanical regulation of intracellular organelle volume, trafficking, and cell homeostasis involving either TPCs or TRPML2.