PLCD4 (phospholipase C delta 4) functions as a non-receptor guanine nucleotide exchange factor that activates the G-protein alpha subunit GNAI3. The gene encodes a phospholipase with both enzymatic activity toward phosphatidylinositol-4,5-bisphosphate and signaling roles at the plasma membrane and cytoplasm. Recent evidence highlights PLCD4's role in cancer biology and immune regulation. In colorectal cancer, lncRNA 60967.1-mediated restoration of PLCD4 expression increases all-trans retinoic acid levels and enhances interferon-gamma-induced apoptosis, reversing IFN-γ resistance and synergizing with anti-PD-1 therapy in murine models 1. In pancreatic ductal adenocarcinoma, PLCD4 expression is directly regulated by p53 and correlates with p53 mutational status, displaying prognostic significance 2. PLCD4 also emerges as a hub gene in acute kidney injury following transplantation, suggesting involvement in transplant-related pathology 3. The gene's transcriptional regulation involves an E-box and AP-1 binding site within its core promoter region, with activity inducible by PKC activation 4. Beyond cancer, PLCD4 shows altered expression in pulmonary arterial hypertension associated with BMPR2 mutations, implicating it in vascular endothelial dysfunction 5. Cattle genetics studies identify PLCD4 as carrying missense variants with substantial fitness impacts 6, highlighting conserved biological importance across species.