PLCB2 encodes phospholipase C beta 2, a phosphatidylinositol-specific phospholipase C that catalyzes production of the second messengers diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) 1. The enzyme preferentially hydrolyzes phosphatidylinositol 4,5-bisphosphate in a calcium-dependent manner and mediates signaling downstream of G protein-coupled receptors (GPCRs), particularly in immune cells 2. In neutrophils, PLCB2 promotes RASGRP4 activation through DAG generation, coupling GPCR activation to Ras and phosphoinositide 3-kinase signaling, which regulates chemotaxis and reactive oxygen species production. Beyond immune function, PLCB2 regulates vascular permeability through control of intracellular calcium flux and phosphatidylinositol 4,5-bisphosphate levels 3. Genetic studies demonstrate that global knockout of PLCB2 blocks VEGF-induced vascular permeability and improves outcomes in hyperoxia-induced lung injury and cardiac ischemia-reperfusion models 3. In melanoma, PLCB2 expression correlates with cell proliferation; knockdown of PLCB2 reduces cell viability and promotes apoptosis by dampening Ras/Raf/MAPK signaling 4. Conversely, in ulcerative colitis, reduced PLCB2 expression contributes to epithelial cell pyroptosis 5. Loss-of-function mutations in PLCB2 associate with primary immunodeficiencies, particularly affecting antibody production and T cell function. NF-κB transcriptionally regulates PLCB2 expression, linking inflammatory signaling to phospholipase C availability 6.