PLCD1 encodes phospholipase C delta 1, an enzyme that produces the second messengers diacylglycerol and inositol 1,4,5-trisphosphate by hydrolyzing phosphatidylinositol 4,5-bisphosphate. This signaling activity is essential for trophoblast and placental development and regulates calcium homeostasis, energy metabolism, and intracellular movement. In cancer biology, PLCD1 functions as a tumor suppressor: its expression is frequently silenced in breast cancer by promoter methylation (detected in 52–78% of cases depending on sample type) 12, and re-expression inhibits proliferation, migration, and cell-cycle progression via apoptosis induction and Wnt/β-catenin pathway suppression 3. Loss-of-function variants cause congenital skin appendage abnormalities including leukonychia totalis and pilomatricomas 45, while a gain-of-function variant (p.Glu396Lys) in familial multiple pilomatricomas increases enzymatic activity, activating protein kinase C/D and extracellular signal-regulated kinase1/2 cascades 6. PLCD1 knockout mice exhibit hair loss and abnormal follicle development, confirming its role in follicle morphogenesis 7. Adenoviral vector-mediated PLCD1 expression shows promise as a gene therapy approach for breast cancer 2.