PHLDA2 (pleckstrin homology like domain family A member 2) is a maternally expressed imprinted gene that exhibits context-dependent dual roles in cellular regulation and disease pathogenesis. In placental development, PHLDA2 functions as a growth regulator, with elevated expression associated with intrauterine growth restriction and serving as a potential diagnostic marker for growth-restricted pregnancies 1. The protein operates through its pleckstrin homology domain to compete with other PH domain-containing proteins for membrane lipid binding, thereby modulating cellular signaling pathways 2. PHLDA2 regulates multiple cellular processes including apoptosis, senescence, and proliferation through mitochondrial-mediated mechanisms and Wnt/β-catenin pathway modulation 3. In cancer biology, PHLDA2 demonstrates complex dual functionality, acting as both tumor suppressor and oncogene depending on cancer type and microenvironment 2 4. The protein promotes drug resistance in hepatocellular carcinoma through AKT pathway activation and immune microenvironment remodeling 5. In trophoblast cells, PHLDA2 interacts with RhoGDI1 to suppress proliferation, migration, and invasion, contributing to preeclampsia pathogenesis 6. These diverse functions highlight PHLDA2's potential as both a diagnostic biomarker and therapeutic target across multiple pathological conditions.