Two-pore channels as master regulators of membrane trafficking and endocytic well-being

Two-pore channels (TPCs) are a ubiquitous class of Ca(2+)- and Na(+)-permeable ion channels expressed within the endo-lysosomal system. They have emerged as central regulators of a wide array of physiological processes intimately linked to information processing. In this short review, we highlight how molecular and chemical strategies have uncovered multiple roles for TPCs in regulating various aspects of endo-lysosomal trafficking associated with disease. We summarise advances in the identification of new small molecules to pharmacologically target TPCs for medical benefit. Lastly, we discuss possible underpinning molecular mechanism(s) that translate TPC-mediated ionic fluxes to function.