CCL21 is a C-C motif chemokine that functions as a critical regulator of lymphocyte trafficking and immune cell migration. Functionally, CCL21 exhibits chemotactic activity preferentially toward naive T cells and dendritic cells rather than B cells, macrophages, or neutrophils, with activity mediated primarily through its cognate receptor CCR7 1. CCL21 is produced predominantly by stromal cells, including myofibroblasts, fibroblasts, and lymphatic endothelial cells 23. Mechanistically, CCL21 binds to CCR7, a G-protein-coupled receptor, activating downstream Gi and G13 signaling pathways 4. Additionally, CCL21 can bind atypical chemokine receptor ACKR4, mediating β-arrestin recruitment. CCL21 expression exhibits circadian regulation, with rhythmic gradients in lymphatic tissues controlling dendritic cell trafficking into lymphatics and affecting adaptive immune responses 5. Clinically, CCL21 dysregulation associates with multiple diseases. In pancreatic cancer, sensory neuron-derived CCL21 promotes cancer cell migration toward nerves, correlating with cancer-associated pain; CCL21 neutralization reduces pain without affecting tumor immunity 6. CCL21 polymorphisms (rs2812378G>A) associate with increased rheumatoid arthritis susceptibility 7, and elevated CCL21/CCR7 axis activity contributes to pathogenesis in multiple autoimmune conditions including Hashimoto's thyroiditis 2. Conversely, in breast cancer and hepatocellular carcinoma, stromal CCL21 expression promotes lymphocyte infiltration and favorable outcomes 38. In coronary artery disease, elevated CCL21 enhances platelet activation and atherothrombosis via CCR7, with CCL21 antibodies showing therapeutic potential 4.