Faculty, Staff and Student Publications

Language

English

Publication Date

1-20-2026

Journal

Cells

DOI

10.3390/cells15020194

PMID

41597268

PMCID

PMC12839299

PubMedCentral® Posted Date

1-20-2026

PubMedCentral® Full Text Version

Post-print

Abstract

The endolysosomal system plays a pivotal role in cellular function. Before reaching lysosomes for degradation, the endocytosed cargoes are sorted at various stages of endosomal trafficking for recycling and/or rerouting. The proper execution of these processes depends on tightly regulated ion fluxes across endolysosomal membranes. Recent studies have demonstrated the importance of two-pore channels (TPCs), including TPC1 and TPC2, in endolysosomal trafficking. These channels are expressed in the membranes of distinct populations of endosomes and lysosomes, where they respond to nicotinic acid adenine dinucleotide phosphate (NAADP) and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2] to conduct Ca2+ and Na+ release from these acidic organelles. Here, we discuss the potential implications of Ca2+ and Na+ fluxes mediated by TPCs across endolysosomal membranes in the physiological and pathophysiological functions of these organellar channels.

Keywords

Humans, Animals, Endosomes, Lysosomes, Calcium Channels, Calcium, Sodium, NADP, Two-Pore Channels, TPCN1, TPCN2, calcium signaling, sodium efflux, fission, fusion, vesicle trafficking, tubulation, osmosis, acidic organelle

Published Open-Access

yes

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