Calcium signaling is a universal mechanism that lets cells convert external and internal cues into precise biochemical responses. At rest, cells keep cytosolic calcium very low compared with the extracellular space and internal stores such as the endoplasmic or sarcoplasmic reticulum. Stimuli open calcium channels at the plasma membrane or in internal membranes, generating highly localized or cell‑wide calcium rises whose amplitude, duration and spatial pattern carry information.

Different channels shape these signals. Voltage‑gated and ligand‑gated channels control calcium entry across the plasma membrane, while IP3 and ryanodine receptors release calcium from stores. Store‑operated calcium entry senses depletion of internal stores and refills them through plasma membrane channels. Pumps and exchangers then restore low resting levels, allowing repeated signaling.

Cells decode calcium signals using proteins that bind calcium and change conformation. Calmodulin, calcineurin, protein kinases and many other sensors translate calcium spikes into changes in gene expression, metabolism, secretion and cell motility. In excitable cells, calcium triggers neuronal transmitter release and couples electrical excitation to contraction in heart and skeletal muscle, where tightly organized microdomains ensure speed and reliability.

Research highlights the importance of spatial organization, including nanometer‑scale junctions between membranes, and of complex temporal patterns such as oscillations and waves. Disrupted calcium homeostasis contributes to cardiovascular disease, neurodegeneration, immune dysfunction and cancer. Emerging tools such as genetically encoded calcium indicators, optogenetic control of channels and high‑resolution imaging are revealing how calcium signals integrate within broader signaling networks. These insights are guiding development of therapies that selectively target calcium channels, pumps or decoding pathways while preserving essential physiological signaling.