CX3CL1 is a unique chemokine subclass, synthesized as a transmembrane molecule It consists of an extracellular NH2-terminal domain, a mucin-like stalk, a transmembrane alpha helix, and a short cytoplasmic tail. CX3CL1 exists in two forms: as a membrane-anchored or as a shed 80-95K glycoprotein. Soluble CX3CL1 is generated by limited proteolysis on the cell surface, and a disintegrin and metallopeptidase 10 (ADAM10) and ADAM17/tumor necrosis factor-alpha-converting enzyme (ADAM17/TACE) participate in this shedding. It has been suggested that ADAM10 acts in the constitutive shedding, and ADAM17 acts in response to cell activation. CX3CL1 is associated with the development of different diseases such as rheumatoid arthritis (RA), rheumatoid vasculitis (RV), Sjögren’s syndrome (SS), systemic lupus erythematosus (SLE), scleroderma, multiple sclerosis, and atherosclerosis. Soluble fractalkine has been detected in the cerebrospinal fluid of patients with neuropsychiatric lupus, and is present at higher levels in the serum of patients with SS, RA, and type 2 diabetes than in control subjects.