ACKR5 (atypical chemokine receptor 5, formerly GPR182) is a non-signaling chemokine receptor expressed primarily on microvascular and lymphatic endothelial cells 1. Unlike classical chemokine receptors, ACKR5 regulates chemokine availability through sequestration, transport, and internalization rather than G-protein activation or calcium mobilization 2. ACKR5 binds a broad chemokine spectrum including CXCL9-14, CCL1, CCL11, CCL19, CCL22-28, and XCL1, with binding affinities below 100 nM 1. Notably, ACKR5 is the sole atypical receptor for CXCL13 and CCL28 2. A defining feature is ACKR5's constitutive, ligand-independent association with β-arrestins, essential for intracellular trafficking and chemokine scavenging 2. ACKR5 cooperates with ACKR3 and ACKR4 to regulate serum chemokine levels 2. Functionally, ACKR5 controls chemokine gradients and modulates immune responses, with genetic ablation affecting spleen size, myelopoiesis, and serum chemokine homeostasis 2. In cancer, ACKR5 expression correlates with IFN-γ-associated inflammatory responses in breast cancer and is overexpressed in prostate cancer tissues 34, suggesting roles in tumor immune microenvironment regulation.