Functions of CX₃CL1 (Fractalkine) contributing to atherogenesis. Membrane-bound CX₃CL1 enables the integrin-independent capture and firm adhesion of leukocytes via the Gαi coupled receptor CX₃CR1. Under inflammatory conditions, cleavage of cell-surface CX₃CL1 by metalloproteinases generates a soluble chemokine, which binds CX₃CR1 on nearby cells and, via signaling intermediates, can induce cell chemotaxis and survival. Thus, CX₃CL1 can have multiple roles in all stages of atherogenesis, including the recruitment, retention, and survival of monocytes in early atherosclerotic lesions as well as foam cell persistence in more advanced plaques. Professional illustration by A. Y. Chen.