C1QTNF4 is a secreted protein with dual C1q domains that regulates inflammatory and metabolic processes through context-dependent mechanisms. Functionally, C1QTNF4 binds to nucleolin as its cell surface receptor on monocytes and B cells, mediating immune modulation 1. The protein inhibits vascular smooth muscle cell proliferation and migration by downregulating the FAK/PI3K/AKT pathway, protecting against neointimal hyperplasia in vascular remodeling 2. In the central nervous system, C1QTNF4 regulates associative learning and memory, with deficiency impairing hippocampal-dependent trace fear conditioning, particularly in females, accompanied by altered expression of learning-related genes 3. C1QTNF4 dysfunction is implicated in multiple diseases. Genetic studies identify C1QTNF4 mutations (p.His198Gln) as SLE risk factors, correlating with early-onset systemic lupus erythematosus 45. The protein functions as a core disease gene in SLE pathogenesis, with mutations inhibiting TNF-dependent NF-κB activation and apoptosis 5. In Alzheimer's disease, transposable element-mediated suppression of C1QTNF4 expression increases neuroinflammation in neurons, identifying it as an anti-inflammatory neuroprotective factor 6. Additionally, C1QTNF4 variants are associated with inherited retinal degeneration 7. The 11p11.2 AD locus contains multiple C1QTNF4-regulating variants affecting amyloid-β and tau pathology 8.