RANK (receptor activator of NF-kappaB) is a member of the tumor necrosis factor (TNF) receptor subfamily that is activated by its ligand, RANKL (TRANCE/OPGL/ODF), to promote survival of dendritic cells and differentiation of osteoclasts. Although RANK is widely expressed, its cell surface expression may be more restricted to dendritic cells and foreskin fibroblasts. RANK contains a 383-amino acid intracellular domain that associates with specific members of the TRAF family to NF-kappaB and JNK activiation. RANKL/RANK signaling may also lead to survival signaling through activation of the Akt pathway and an upregulation of survival proteins, including Bcl-xL. RANK signaling has been implicated as a potential therapeutic to inhibit bone loss and arthritis.
