PLCB3 (phospholipase C beta 3) is a key signal transduction enzyme that catalyzes production of second messengers diacylglycerol and inositol 1,4,5-trisphosphate, primarily activated downstream of G protein-coupled receptors through G(q)/G(11) alpha proteins 12. The gene, located on chromosome 11, contains 31 exons spanning approximately 15 kb with a 4.4 kb transcript 34. PLCB3 plays critical roles in multiple physiological processes. Large-scale genetic studies identified PLCB3 as a candidate gene for blood pressure regulation, with rare variants showing ~8-fold larger effects than common variants 5. In the cerebellum, PLCB3 serves as a neuroplasticity marker, exhibiting distinct compartmentalization patterns in primate cerebellar cortex and nuclei 6. Disease relevance is substantial. PLCB3 acts as a tumor suppressor in neuroendocrine cancers, with low expression correlating with neoplastic phenotype, and its restoration inhibiting cell growth and tumorigenicity 7. In colorectal cancer, PLCB3 represents an oncogenic driver, with high expression predicting poor prognosis; cetuximab treatment inhibits CRC progression partly through PLCB3 modulation 8. Bipolar disorder fine-mapping identified PLCB3 among genes involved in neurotransmission and neurodevelopment 9. In ulcerative colitis, PLCB3 downregulation suggests loss of intestinal homeostatic function 10.