LRP8 (LDL receptor-related protein 8) is a multifunctional endocytic receptor with critical roles in viral pathogenesis, metabolic regulation, and cancer progression. As a primary function, LRP8 acts as a high-affinity receptor for tick-borne encephalitis virus (TBEV), mediating viral attachment and internalization through its LDLR type A domains 1-2, facilitating central nervous system infection 12. Beyond viral entry, LRP8 serves as a selenoprotein P receptor essential for selenium-dependent antioxidant defense; in MYCN-amplified neuroblastoma, LRP8-mediated selenocysteine uptake protects cells from ferroptosis, making LRP8 downregulation a therapeutic vulnerability 3. LRP8 promotes cancer progression through multiple mechanisms: in gastric cancer, H. pylori-induced LRP8 overexpression facilitates β-catenin nuclear translocation and cancer stem cell enrichment 4; in breast cancer, Reelin-LRP8 signaling activates CDC42 to promote abluminal migration and brain metastasis 5; in multiple myeloma, LRP8-dependent cholesterol uptake activates mTORC1 signaling while suppressing apoptosis 6. Genetically, LRP8 variants associate with gastrointestinal and psychiatric disorders through shared pleiotrophic pathways involving synaptic function and cell adhesion 7. These findings establish LRP8 as both a viral receptor and metabolic hub with therapeutic implications for infectious diseases and multiple malignancies.