XCL1, also known as lymphotactin, is an inflammatory chemokine secreted by T cells and natural killer (NK) cells. Early reports described XCL1 as a mediator of T cell and NK cell migrations, but recent studies suggest a highly specialized role for XCL1 and its receptor XCR1. The XCL1-XCR1 axis has been shown to play an important role in dendritic cell mediated cytotoxic immune response and in the formation of self-tolerance mechanisms through the development of regulatory T cells within the thymus. XCL1 also acts as a conformation-dependent inhibitor of HIV-1. Unlike other chemokines, XCL1 conformation interchanges between conserved chemokine folds and an unrelated dimeric structure under physiological conditions. The XCL1 monomer binds XCR1 with a high affinity, whereas the dimer form binds glycosaminoglycan (GAG) with high affinity, but fails to activate XCR1. Human XCL1 encodes a 114 amino acid precursor protein with a 21 amino acid signal peptide and a single disulfide bond.