CCL4L2 is a C-C motif chemokine that functions as a potent immunomodulatory mediator in multiple pathological contexts. As a chemokine, CCL4L2 induces chemotaxis of cells expressing CCR5 or CCR1 receptors and inhibits HIV replication in CCR5-expressing peripheral blood monocytes [UniProt]. Beyond its classical antiviral role, CCL4L2 has emerged as a key inflammatory mediator in immune-driven diseases. In immune checkpoint inhibitor-induced myocarditis, CCL4L2 is upregulated in clonally expanded cytotoxic CD8+ Temra cells, facilitating recruitment of innate immune cells including monocytes, macrophages, and neutrophils to cardiac tissue, contributing to cardiotoxicity 1. CCL4L2 expression is associated with corticosteroid-nonresponsive asthma, particularly in neutrophil-mediated airway inflammation, with expression negatively correlating with pulmonary function improvement after inhaled corticosteroid treatment 2. In rheumatoid arthritis synovium, CCL4L2 is upregulated in macrophage subsets via NF-κB signaling, promoting inflammatory responses 3. In tendinopathy, CCL4L2+ M1 macrophages promote inflammatory responses and inhibit tendon stem/progenitor cell differentiation 4. Additionally, CCL4L2 participates in gut dysbiosis-driven inflammatory bowel disease through the CCL4L2-VSIR axis 5, and is expressed in cytotoxic CD4+ T cells in radiation-induced brain injury 6. Collectively, CCL4L2 represents a therapeutic target across multiple immune-mediated pathologies.