ALPP (alkaline phosphatase, placental) is a phosphate ester-hydrolyzing enzyme that functions as a cell surface glycoprotein with magnesium and zinc ion binding capabilities 1. The gene is located at chromosome 2 2. ALPP serves as a tissue-specific alkaline phosphatase isoenzyme normally expressed during pregnancy, but shows aberrant upregulation in various malignancies including germ cell tumors, cholangiocarcinoma, and mesothelioma 34. In cancer contexts, ALPP functions as a tumor-specific antigen suitable for CAR-T cell therapy targeting, particularly in solid tumors like mesothelioma and ovarian cancer 3. The protein demonstrates immunomodulatory properties, with transgenic overexpression compromising phagocytic function and affecting both innate and adaptive immune responses 5. ALPP expression correlates with poor prognosis in cholangiocarcinoma patients and is associated with PI3K-Akt signaling pathway activation and immune evasion mechanisms 4. Additionally, ALPP serves as a component of proteomic signatures associated with smoking-related morbidity and mortality 6. The gene's expression is regulated by methylation status, with hypomethylation leading to upregulation in pathological conditions 4.