ALPP/ALPPL2 proteins are members of the alkaline phosphatase family, which are closely related and regulated GPI-anchored proteins. ALPP, also known as placental alkaline phosphatase, and ALPPL2, also known as germ cell alkaline phosphatase or placental-like alkaline phosphatase 2, share a high degree of amino acid sequence similarity (98% homology) and have a highly restricted tissue expression pattern, primarily found in placental trophoblasts and certain tumor tissues. ALPPL2 is expressed in various cancers, including mesothelioma, ovarian cancer, and gastric cancer, and is considered a tumor-specific antigen due to its high tissue specificity. This makes it a promising target for cancer therapies, such as antibody-drug conjugates and CAR-T cell therapies.