Ion Channels of the Plasma Membrane and Endolysosomes: Roles in Osmoregulation and Volume Regulation in Immune Cells

Maintenance of cellular volume is essential for cell homeostasis. Immune cells experience marked osmotic changes during activation and migration, and these challenges are intensified by local osmotic fluctuations characteristic of inflammatory disease progression. Beyond cellular osmoregulation, endolysosomal compartments also undergo volume regulation during endocytic processes-including phagocytosis and macropinocytosis-which integrate osmotic cues that are critical for immune cell activation and function. This review provides a comprehensive overview of the molecular mechanisms by which ion channels of the plasma membrane and endolysosomal compartments orchestrate cellular and organelle volume regulation, respectively. We first summarize the diverse families of ion channels, aquaporins, and associated signaling pathways that maintain cell volume homeostasis, highlighting their roles in innate and adaptive immunity as well as inflammation-related diseases. Furthermore, we discuss how endolysosomal ion channels contribute to the regulation of phagocytosis and macropinocytosis pathways and modulate host-pathogen interactions. Collectively, these insights underscore the importance of ion channels as integrators of osmotic signals that sustain immune cell function and represent potential targets for immunomodulatory therapies.