Because of the important role of NF-κB in osteoclasts, specific IKBKG mutation sites can also lead to a special type of EDA-ID, namely osteopetrosis, lymphedema, EDA, and immunodeficiency (OL-EDA-ID, OMIM 300301),8 this is the most severe clinical phenotype caused by hypomorphic mutations in IKBKG. Current understanding suggests that osteopetrosis caused by IKBKG mutations results from impaired activation of the IKK complex in osteoclasts, disrupting their differentiation and function, and causing an imbalance between bone formation and resorption.9 This evidence concerns the gene NFKB1 and hypohidrotic ectodermal dysplasia.