RANK is the receptor for RANK-Ligand (RANKL) and part of the RANK/RANKL/OPG signaling pathway that regulates osteoclast differentiation and activation.

The cytoplasmic domain of RANK binds TRAFs 1, 2, 3, 5, and 6 which transmit signals to downstream targets such as NF-κB and JNK.

[6] There are two monomers of RANK related by noncrystallographic 2-fold symmetry perpendicular to the long axis of the molecules in the asymmetric unit.

This key role of the RANK-RANKL system may link the osteoporosis and hot flashes seen as symptoms of hormonal changes in post-menopausal women.

Calcium transferred from mother to fetus and neonate is provided by the degradation of the female bone by increased osteoclastic activity, which is regulated by the RANK/RANKL axis.

RANKL also works through RANK to provide proliferative and survival signals to promote the final stages of lactating mammary gland development.

Dysfunctional RANK or RANKL causes the arrest of differentiation and expansion of the alveolar bunds into mature lobulo-alveolar mammary structures, disabling the production of milk.

[11] Another study looked into developing small mimetics based on the structure of OPG that bind to RANK as well as RANKL and cause defective coupling between the two.

[17] RANK has been shown to interact with: This article incorporates text from the United States National Library of Medicine, which is in the public domain.