Atypical chemokine receptor 4 (ACKR4)

Atypical chemokine receptor 4 (ACKR4) is a member of the G protein-coupled receptor family that does not activate typical G protein-coupled signaling upon ligand binding. Instead, ACKR4 binds and internalizes several CC-type chemokines, including CCL19, CCL21, and CCL25—removing them from the extracellular environment and delivering them to cellular degradation pathways. This mechanism fine-tunes chemokine gradients that regulate the positioning and migration of leukocytes, playing a critical role in immune homeostasis, inflammation resolution, and tissue-specific immune cell trafficking. ACKR4 functions as a regulatory checkpoint for chemokine availability, influencing processes in skin, lymph nodes, gut, and other tissues. Loss or pharmacological blockade of ACKR4 can result in chemokine accumulation and abnormal immune cell distribution. Unlike classical chemokine receptors, ACKR4 primarily recruits β-arrestins rather than G-protein signaling. Its emerging roles include modulation of cancer progression, immune deficiency diseases, and potentially pulmonary arterial hypertension [1][2][3][4][6].

Other names

CCX CKRCKR-11CCR-11CCR11CCX-CKRPPR1VSHK1CC-CKR-11CCBP2CC chemokine receptor-like 1Chemokine (C-C motif) receptor-like 1Chemocentryx chemokine receptorOrphan seven-transmembrane receptor

For theoretical/scientific drug targeting: Blockers or antagonists would inhibit chemokine scavenging, increasing local chemokine concentrations. Agonists or custom ligands could enhance scavenging activity. Therapeutic modulation may alter immune cell migration and inflammation [3][4]