In 1997, a glycoprotein was isolated that blocked osteoclast differentiation from precursor cells. This protein prevented osteoporosis when administered to ovariectomized rats, and led to osteopetrosis when overexpressed. This newly discovered protein was named osteoprotegerin (OPG). The discovery of osteoprotegerin has stimulated a great deal of work in the fields of endocrinology, rheumatology and immunology, and resulted in the further discovery of two other members of the TNF receptor superfamily: the receptor activator of nuclear factor Kss (RANK) and osteoprotegerin ligand (OPG-L or RANKL). To date, however, relatively little is still known about OPG/ RANKL/ RANK.