Here, we report postnatal phenotypic changes of calvarial bone in Eda1-deficient mice and the impact of Eda1 deficiency on osteoclastic differentiation in vitro, identifying diminished nuclear Nfatc1 and bone-resorbing enzymes as a key feature that probably underlies osteopetrosis-like changes in Eda1-deficient murine calvariae. Here, EDA is linked to osteopetrosis.