Siglec-15 was reported to induce Akt activation by interacting with DAP12.3 Mice lacking ITAM harboring adapters, Fc receptor common γ (FcRγ), and DAP12 exhibit severe osteopetrosis owing to impaired osteoclast differentiation.25 Activation of osteoclast-associated receptor/FcRγ signaling rescued impaired osteoclastogenesis in Siglec-15-deficient cells.2 These findings suggest that in addition to promoting osteoclast fusion, the Siglec-15 signaling pathway plays a critical role in osteoclastogenesis. Here, TYROBP is linked to osteopetrosis.