Calcium signaling in microglial immune functions: current understanding and implications for disease.

Microglia are the resident innate immune cells of the brain that play essential roles in immune surveillance, phagocytosis, and neuroinflammatory responses. A central regulator of these diverse functions is intracellular Ca2+ signaling, which connects extracellular cues to transcriptional and metabolic programs that shape microglial activation states. Recent advances have expanded understanding of the 'Ca2+ toolkit' in microglia, which includes P2X and P2Y receptors, Orai Ca2+ channels, transient receptor potential channels, inositol triphosphate receptors, and organellar Ca2+ handling systems. These pathways generate dynamic and spatially localized Ca2+ signals that regulate numerous effector functions, including process motility, cytokine production, phagocytosis, metabolism, and communication with other brain cells. Emerging evidence further identifies dysregulated Ca2+ signaling as a key driver of chronic neuroinflammation in brain disorders. Here, we review the major components of the microglial Ca2+ signaling toolkit, discuss their molecular mechanisms and physiological functions, and highlight contributions to neuroinflammatory diseases.