PLCB1 (phospholipase C beta 1) is a phospholipid hydrolase that catalyzes the breakdown of phosphatidylinositol 4,5-bisphosphate into diacylglycerol and inositol 1,4,5-trisphosphate, mediating intracellular signaling downstream of G protein-coupled receptors 1. Beyond its canonical lipid signaling role, PLCB1 functions as an oncogenic driver in multiple cancers through diverse mechanisms. In cholangiocarcinoma, PLCB1 activates PI3K/AKT signaling to promote epithelial-mesenchymal transition (EMT) and chemotherapy resistance 2. Similarly, in gastric cancer, PLCB1 enhances migration and invasion via actin cytoskeletal remodeling and AKT-mediated EMT 3. In gliomas, PLCB1 suppresses Wnt/β-catenin signaling; increased oxygen stimulation downregulates PLCB1 via miR-1290, leading to β-catenin accumulation and chemoresistance 4. In myelodysplastic neoplasms, elevated PLCB1 expression correlates with transformation to acute myeloid leukemia, and PLCB1 inhibition suppresses leukemic cell proliferation 5. PLCB1 is also implicated in hepatocellular carcinoma through YAP1-dependent arachidonic acid metabolism 6. Additionally, PLCB1 appears relevant to metabolic and immunological diseases, identified in sarcopenia-type 2 diabetes pathways and anti-TNFα therapy response in Crohn's disease 78. Clinical significance includes potential therapeutic targeting via AKT and Wnt inhibitors.