CD163 is a macrophage-specific scavenger receptor that functions as a key regulator of hemoglobin homeostasis and immune tolerance. The receptor binds haptoglobin-hemoglobin complexes through calcium-dependent interactions involving acidic residues, facilitating their endocytosis and preventing oxidative damage from free heme iron 1. CD163 assembles into trimeric and dimeric structures that enhance ligand capture 1. Upon shedding, the soluble extracellular domain (sCD163) serves as a macrophage activation marker with multiple biological roles, including hemoglobin scavenging, cytokine sequestration, and paracrine signaling 2. sCD163 levels correlate with disease severity in chr12 inflammatory conditions (atherosclerosis, asthma, rheumatoid arthritis), acute infections (sepsis, hepatitis, malaria), and metabolic disorders 2. The TWEAK/Fn14/CD163 axis regulates immune signaling and metabolic homeostasis, with CD163 scavenging soluble TWEAK 3. Clinically, CD163+ macrophages exhibit context-dependent roles. In atherosclerosis, CD163+ macrophages restrain vascular calcification through NF-κB-induced hyaluronan synthase expression, promoting high-risk plaque development 4. Conversely, CD163+ dendritic cells (DC-10) produce IL-10 and promote regulatory T cell differentiation, supporting immune tolerance 5. However, CD163 drives protumoral macrophage activation in sarcomas via IL-6 production, correlating with poor survival 6. CD163 polymorphisms associate with acute myeloid leukemia susceptibility and prognosis 7.