Swine CX3CL1 (C-X3-C motif chemokine ligand 1), also known as fractalkine, is a chemokine belonging to the CX3C chemokine family, characterized by three amino acids separating the first two conserved cysteine residues. CX3CL1 is unique among chemokines because it exists in both a membrane-bound form and a soluble form, allowing it to function in both leukocyte adhesion and chemotaxis. In pigs (Sus scrofa), CX3CL1 is produced primarily by endothelial cells, epithelial cells, neurons, and macrophages in response to infection, inflammatory cytokines, or tissue injury. CX3CL1 binds to its receptor CX3CR1, which is expressed on monocytes, macrophages, natural killer (NK) cells, and subsets of T lymphocytes, promoting adhesion, migration, and activation of immune cells at sites of inflammation. In swine health, the CX3CL1–CX3CR1 pathway contributes to immune responses during respiratory and systemic infections, including diseases such as porcine reproductive and respiratory syndrome virus (PRRSV) and swine influenza, where chemokine-mediated leukocyte recruitment helps coordinate inflammatory and antiviral responses in lung tissues. Because pigs share important physiological and immunological similarities with humans, swine CX3CL1 is also studied in translational animal models of cardiovascular disease and inflammatory disorders, particularly in atherosclerosis models, where fractalkine signaling plays a role in monocyte adhesion to vascular endothelium and vascular inflammation.