Macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-B ligand (RANKL)-evoked cellular signaling are essential for osteoclastogenesis (Fig. 7).131,132 Similar to OBs, PYP is pivotal in regulating OC development and function, and dysregulation of PYP in OCs leads to osteopetrosis, osteoporosis, osteolysis, and bone metastasis of soft tissue cancers.132 Below, we review 14 PTPs involved in osteoclastogenesis and OC-related skeletal diseases in humans and mice. The gene discussed is TNFSF11; the disease is osteopetrosis.