Atypical chemokine receptor 4 (ACKR4) controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting instead in chemokine sequestration, degradation, or transcytosis. Chemokine-binding does not activate G-protein-mediated signal transduction but instead induces beta-arrestin recruitment, leading to ligand internalization. ACKR4 plays an important role in controlling the migration of immune and cancer cells that express chemokine receptors CCR7 and CCR9, by reducing the availability of CCL19, CCL21, and CCL25 through internalization. ACKR4 negatively regulates CXCR3-induced chemotaxis and regulates T-cell development in the thymus. References: The UniProt Consortium. Nucleic Acids Res. 47: D506-515 (2019); Nucleic Acids Res. 2016 Jan 4;44(D1):D733-45, PMID:26553804