LRP1 (Low-Density Lipoprotein Receptor-Related Protein 1) is a multifunctional endocytic/signaling cell-surface receptor that regulates diverse cellular processes including endocytosis, protein trafficking, and cell survival 1. Functionally, LRP1 mediates receptor-ligand interactions through its cargo receptor activity and clathrin-dependent endocytosis, enabling internalization of diverse substrates including amyloid-β, tau, and α-synuclein 23. In the nervous system, LRP1 plays critical roles in neurodegeneration: it controls tau uptake and prion-like spread in tauopathies 2, facilitates α-synuclein internalization and propagation in Parkinson's disease 3, and promotes amyloid-β clearance across the blood-brain barrier in Alzheimer's disease 4. LRP1 also mediates astrocyte-to-neuron mitochondrial transfer, protecting against ischemic stroke by suppressing ARF1 lactylation 1. Beyond neurodegeneration, LRP1 serves as a host entry receptor for viral pathogens including Rift Valley fever virus and Pseudomonas aeruginosa exotoxin A 5. In cancer, tumor cell LRP1 promotes metastatic progression through MDK signaling in gastric cancer ovarian metastases 6 and PCSK9-mediated regulation in breast cancer metastasis 7. These findings establish LRP1 as a pivotal regulator of pathological protein spread and cellular homeostasis with significant therapeutic potential.