ACKR4 (atypical chemokine receptor 4) is an unconventional chemokine receptor that functions as a scavenger rather than a traditional signaling receptor 1. Unlike classical chemokine receptors, ACKR4 binds high-affinity ligands (CCL19, CCL21, CCL25, CXCL13) without activating G-protein signaling; instead, it recruits β-arrestin to mediate chemokine internalization and degradation 2. This chemokine sequestration controls immune cell migration by regulating the availability of ligands for chemokine receptors CCR7 and CCR9, and negatively regulates CXCR3-induced chemotaxis 3. ACKR4 plays critical roles in immune homeostasis, including T-cell thymic development and lymphocyte trafficking in secondary lymphoid organs 4. In disease contexts, ACKR4 exhibits complex functions: it acts as a protective immune checkpoint in pulmonary arterial hypertension, where downregulation correlates with increased pro-inflammatory immune infiltration 5. In cancer, ACKR4 predominantly functions as a tumor suppressor, particularly in Burkitt lymphoma and breast cancer, where reduced expression associates with increased metastatic potential 67. ACKR4 represents a promising therapeutic target for inflammatory and malignant diseases 1.