TPBG (trophoblast glycoprotein) is a leucine-rich repeat adhesion protein localized to the cell surface and plasma membrane 1 that functions as a negative regulator of canonical Wnt/beta-catenin signaling 2. The protein inhibits Wnt signaling by blocking Wnt3a-dependent LRP6 internalization 2. In vascular biology, TPBG orchestrates pericyte migration and angiogenesis through hypoxia-dependent upregulation via the CXCL12/CXCR7/ERK1/2 signaling axis 3. TPBG is also expressed in retinal rod bipolar cells where it may maintain functional synapses, with expression strongly dependent on TRPM1 1. Clinically, TPBG overexpression contributes to preeclampsia pathogenesis by disrupting trophoblast migration and invasion, impairing spiral artery remodeling 4. TPBG is identified as a key inflammation-associated genetic biomarker for preeclampsia prediction 5. In oncology, TPBG is recognized as an oncofoetal antigen expressed by many cancers but rarely in normal adult tissues, promoting epithelial-mesenchymal transition and cancer cell spread 2. TPBG expression is significantly elevated in treatment-resistant HER2+ breast cancer, representing a negative biomarker for pathological complete response 6. These findings establish TPBG as a multifunctional protein with therapeutic potential as both a diagnostic biomarker and immunotherapy target.