F4/80, also known as EGF-like module-containing mucin-like hormone receptor-like 1 (EMR1), is a cell surface glycoprotein that is a member of the EGF-TM7 protein family. It is primarily used as a marker for mature macrophages in mice and shows significant expression changes during the maturation and activation of these cells. F4/80 is expressed on various mature macrophage populations, including Kupffer cells, Langerhans cells, microglia, and macrophages located in the peritoneum, intestinal lamina propria, splenic red pulp, lung, thymus, and bone marrow stroma. This antigen is encoded by the Adgre1 gene, which is a seven transmembrane G protein-coupled receptor with an extracellular domain containing repeated Epidermal Growth Factor (EGF)-like calcium binding domains. The F4/80 antigen is not only crucial for the phenotypic characterization of macrophages but also plays a role in immune regulation, as indicated by studies showing its necessity for inducing CD8+ regulatory T cells responsible for peripheral immune tolerance.