Schematic diagram of variety of pathways for Ca²⁺ across the plasma membrane and internal membranes [adapted from (4 )]. Plasma membrane-bound Ca²⁺ channels: voltage-gated calcium channels (VGCC), receptor potential (TRP) channels, ligand-gated ionotropic P2X receptors (P2X), mechanosensitive Piezo channels (Piezo). Plasma membrane-bound channels (store-operated Ca²⁺ entry pathway) mediated by stromal interaction molecule 1 (STIM1) sensor and ORAI1 channels. Internal membrane-bound channels: ryanodine receptor (RYR) and inositol 1,4,5-trisphosphate receptor (IP3R), IP3 ligand produced by the plasma membrane G protein-coupled receptor (GPCR) via Gaq and phospholipase C-β (PLCβ) proteins (not shown). Two-pore channels (TPC) regulate Ca²⁺ release from lysosomes. Mitochondrial Ca²⁺ levels are controlled by mitochondrial calcium uniporter (MCU) complex and mitochondrial Na⁺/Ca²⁺ exchanger (NCLX). Ca²⁺ pumps (shown stippled and with a curved arrow to indicate the conversion of ATP to ADP and consequent release of energy to drive the Ca²⁺ against an electrochemical gradient): Plasma membrane Ca²⁺-ATPase (PMCA), sarcoplasmic/endoplasmic reticulum Ca²⁺-ATPase (SERCA), Golgi network secretory pathway Ca²⁺/Mn²⁺-ATPase (SPCA). Full straight arrows indicate Ca²⁺ flux; dashed arrows: Na⁺ flux.