VLDLR (very low density lipoprotein receptor) is a cell surface receptor that primarily functions in lipoprotein metabolism and neuronal signaling. The receptor binds and internalizes apoE- and apoB-containing lipoproteins, including LDL and VLDL, regulating their cellular uptake and contributing to cholesterol homeostasis 1. In the nervous system, VLDLR serves as a core component of the Reelin signaling pathway alongside ApoER2, facilitating neuronal migration, dendritic growth and branching, synaptogenesis, and synaptic plasticity during brain development and maturation 2. VLDLR also functions as a viral receptor, with recent studies identifying it as a receptor for multiple alphaviruses including Semliki Forest virus, eastern equine encephalitis virus, and Sindbis virus 3. Disease relevance includes cerebellar ataxia and intellectual development disorders, while a protective variant (RELN-COLBOS) that enhances VLDLR/ApoER2 signaling has been associated with resilience to Alzheimer's disease 4. In pathological contexts, VLDLR promotes lipid metabolism in pancreatic stellate cells, contributing to pancreatic fibrosis through IL-33-mediated inflammatory responses 5, and its signaling pathway disruption is implicated in various neurological disorders including autism, schizophrenia, and epilepsy 2.