CX3C motif chemokine receptor 1 (CX3CR1), also known as the fractalkine receptor or G-protein coupled receptor 13 (GPR13), is a transmembrane protein of the G protein-coupled receptor 1 (GPCR1) family and the only known member of the CX3C chemokine receptor subfamily. As the name suggests, this receptor binds the inflammatory chemokine CX3CL1 (also called neurotactin in mice or fractalkine in humans). This endogenous ligand solely binds to CX3CR1 receptor. Interaction of CX3CR1 with CX3CL1 can mediate migration, adhesion and retention of leukocytes, because Fractalkine exists as membrane-anchored protein (mCX3CL1) as well as cleaved soluble molecule (sCX3CL1) due to proteolysis by metalloproteinases (MPPs). The shedded form carries out typical function of conventional chemokines, the chemotaxis, while the membrane-bound protein behaves as adhesion molecule for facilitation of diapedesis. Both partners of CX3CL1-CX3CR1 axis are present on numerous cell types from hematopoietic and nonhematopoietic cells throughout the body. Moreover, their distinct cell expression is dependent on specific tissues and organs, which provides broad sphere of biological activity. Hence, considering their various functional activity, they are also linked with multiple neurodegenerative and inflammatory disorders as well as with tumorigenesis. Genetics The coding gene for CX3CR1 is now officially called identically to its protein: CX3CR1 gene, but may be still referred to by other older names such as V28; CCRL1; GPR13; CMKDR1; GPRV28; CMKBRL1. A genome location of the gene in humans is on the short arm of the chromosome 3p22.2. It is composed of four exons (only one contains coding region) and three intronic elements. Expression of the genomic sequence is regulated via three promoters. Two missense mutations in CX3CR1 gene, variants of single nucleotide polymorphism (SNP) of the receptor, are responsible for functional change of the protein. Names of these variants are derived from given substitution and its position: valine to isoleucine (V249I) and threonine to methionine (T280M). Polymorphism of CX3CR1 has been linked to diseases relating to cardiovascular system (e.g. Atherosclerosis), nervous system (e.g. Alzheimer's disease, Sclerosis) or infections (e.g. systemic candidiasis. Orthologs of CX3CR1 gene are found among animals, especially in mammals with high functional similarity, namely chimpanzee, dog, cat, mouse and rat. Orthologs are located on chromosome 9qF4 in the mouse genome and in the rat 8th chromosome on position 8q32. Expression CX3CR1 is expressed constitutively or in inflammatory response in various cells from hematopoietic lineage: T lymphocytes, natural killer (NK) cells, dendritic cells, B lymphocytes, mast cells, monocytes, macrophages,