PLCD3 is a phospholipase C isoform that hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) to generate second messengers diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3), activating protein kinase C and releasing intracellular calcium stores. Beyond its canonical signaling role, PLCD3 has emerged as a prominent oncogenic factor across multiple cancer types. In thyroid cancer, PLCD3 overexpression promotes proliferation, migration, and invasion while inhibiting apoptosis through the Hippo pathway, with expression correlating to metastasis risk 1. Similar pro-tumorigenic functions occur in esophageal squamous cell carcinoma via PI3K/AKT/P21 signaling 2, nasopharyngeal carcinoma through flotillin2 interaction 3, and osteoarthritis progression via miR-34a-5p regulation of the PI3K/AKT pathway 4. Clinically, PLCD3 exhibits potential as a cancer biomarker and therapeutic target. Beyond malignancy, PLCD3 mutations contribute to congenital hemifacial microsomia 5, and lncRNA PLCD3-OT1 protects against age-related cataracts by regulating PLCD3 expression through miR-224-5p sponging 6. Recent proteomics identified PLCD3 as a sex-interactive protein in Alzheimer's disease cognitive trajectories 7, suggesting broader neurobiological significance.