CCRL2 (C-C motif chemokine receptor-like 2) is a non-signaling atypical chemokine receptor that functions primarily as a chemerin and CCL19 ligand presenter rather than a conventional G protein-coupled receptor 1. Unlike its signaling counterpart CMKLR1, CCRL2 lacks classical G protein-coupled signaling capabilities but instead captures and internalizes chemokines, presenting them to functional signaling receptors on immune cells 2. CCRL2 is predominantly expressed by barrier cells including lung capillary endothelial cells, epithelial cells, and certain immune populations 3. Functionally, CCRL2 plays a critical role in leukocyte recruitment and immune regulation. In cardiovascular disease, CCRL2+ macrophages exhibit a pro-inflammatory, TNF-α-responsive phenotype that promotes cardiac remodeling and heart failure; parasympathetic stimulation via α7nAChR signaling specifically suppresses these cells through NRF2-mediated mechanisms 4. In cancer immunology, CCRL2 expression on lung endothelium controls natural killer cell homing and tumor surveillance through the chemerin/CMKLR1 axis, with reduced CCRL2 promoting tumor progression 3. In allergic rhinitis, CCRL2 emerges as a key diagnostic and inflammatory response-associated gene 5. These findings position CCRL2 as a potential therapeutic target for modulating immune responses in cardiac disease, cancer, and allergic inflammation.