EDARADD is an adapter protein that mediates ectodysplasin (EDA) receptor signaling during ectodermal organ development. 1 It couples EDAR death domain activation to downstream NF-κB pathway activation, which regulates transcription of genes controlling ectodermal appendage development. 1 EDARADD is essential for proper morphogenesis of hair, teeth, nails, and sweat glands during development. 2 Pathogenic EDARADD variants cause hypohidrotic ectodermal dysplasia (HED), an autosomal dominant or recessive disorder characterized by sparse hair, hypohidrosis, hypodontia, and nail abnormalities. 3 4 Mutations congregate in exons encoding key functional domains, with EDARADD accounting for approximately 10% of genetically characterized ED cases. 2 Beyond developmental roles, EDARADD has emerged as an oncogenic factor in epithelial malignancies. In colon cancer, elevated EDARADD promotes epithelial-mesenchymal transition (EMT) and cell proliferation by stabilizing the transcriptional repressor Snail1 through suppression of the E3 ligase Trim21, while activating NF-κB signaling. 5 Similarly, in bladder cancer, EDARADD silencing suppresses proliferation, migration, and EMT through MAPK pathway repression. 6 These findings identify EDARADD as an emerging therapeutic target in cancer.