Although no mutations have been identified in CRELD2 to date, these data highlight a novel role for CRELD2 in osteoclastogenesis and indicates CRELD2 may be a potential genetic locus for skeletal diseases caused by dysregulated osteoclast differentiation and function, such as osteogenesis imperfecta or osteoporosis. Here, CRELD2 is linked to osteogenesis imperfecta.