Alkaline phosphatase, germ cell (ALPG) (ALPG)

Alkaline phosphatase, germ cell (ALPG), also known as ALPPL2 or ALPP2, is a glycosylphosphatidylinositol (GPI)-anchored membrane-bound enzyme belonging to the alkaline phosphatase family. It is primarily expressed in placental trophoblasts and germ cells during development but remains largely silent in normal adult tissues, making it a highly specific oncofetal antigen. In various malignancies, including mesothelioma, ovarian cancer, and seminoma, ALPPL2 is significantly overexpressed on the cell surface, where it promotes tumor cell proliferation and survival. Due to its restricted normal tissue distribution and high tumor specificity, it has emerged as a promising therapeutic target for antibody-drug conjugates (ADCs), CAR-T cell therapies, and diagnostic imaging. Current drug development efforts focus on leveraging its rapid internalization properties to deliver potent cytotoxic payloads directly into cancer cells while minimizing off-target toxicity.

Other names

ALPPL2ALPP2GCAPGerm cell alkaline phosphatasePlacental-like alkaline phosphatase 2Nagao isozyme

Antibody-drug conjugates (ADCs) targeting ALPPL2 deliver cytotoxic payloads directly to tumor cells upon internalization. Chimeric antigen receptor (CAR) T-cell therapies utilize anti-ALPPL2 scFvs to direct T-cell mediated killing of cancer cells. Small molecule inhibitors and aptamers are also being explored to block the enzyme's dephosphorylating activity.