Atypical chemokine receptor 2 (ACKR2)

Atypical chemokine receptor 2 (ACKR2, also known as D6 or CCBP2) is a seven-transmembrane G protein-coupled receptor belonging to the atypical chemokine receptor family[1][4]. It binds and internalizes multiple inflammatory CC chemokines, especially those involved in leukocyte recruitment and inflammatory signaling[1][3]. Unlike canonical chemokine receptors, ACKR2 does not couple to G proteins for classical chemotactic signaling but instead employs β-arrestin-dependent pathways to mediate chemokine scavenging and receptor recycling[3][4]. ACKR2 is expressed primarily on lymphatic endothelial cells, some leukocytes, trophoblasts, and myeloid cells, and serves as a "decoy" or clearance receptor, shaping chemokine gradients and limiting inappropriate leukocyte infiltration[3][4]. It is implicated in regulating inflammation, tumor microenvironment dynamics, immune homeostasis, and certain pregnancy outcomes. Downregulation or loss-of-function mutations are associated with increased inflammation and cancer risk, while its role in cancer is nuanced, acting as both a tumor suppressor and a potential facilitator of immune escape in varying contexts[1][3]. There are currently no approved drugs specifically targeting ACKR2.

Other names

D6CCBP2Chemokine-binding protein 2Chemokine-binding protein D6Atypical chemokine receptor D6

Ligand binding and scavenging/inactivation of inflammatory CC chemokines (such as CCL2, CCL3, CCL4, CCL5, CCL7, CCL8, CCL11, CCL13, CCL14, CCL17, CCL22); Internalization and lysosomal degradation of chemokine ligands; β-arrestin-dependent (not G protein) signaling to regulate receptor surface levels and scavenging efficacy