X‑linked Ectodysplasin Receptor (XEDAR), also known as EDA2R and TNFRSF27, is an approximately 45 kDa transmembrane protein in the TNF receptor superfamily (1). Mature mouse XEDAR consists of a 138 amino acid (aa) extracellular domain (ECD) with three tandem TNFR cysteine‑rich domains, a 21 aa transmembrane segment, and a 138 aa cytoplasmic domain. Within the ECD, mouse XEDAR shares 87% and 96% aa sequence identity with human and rat XEDAR, respectively. A 20 kDa fragment of the ECD can be shed by metalloprotease mediated cleavage (2). XEDAR binds selectively to the EDA‑A2 variant of Ectodysplasin (EDA), while the closely related receptor EDAR binds selectively to the EDA‑A1 variant (3). Other than a 2 aa deletion in its TNF‑like domain, EDA‑A2 is identical to EDA‑A1 (3). Mutations in both EDAR and EDA are associated with hypohidrotic ectodermal dysplasia (HED), a disorder of hair, tooth, and eccrine sweat gland morphogenesis (4). XEDAR itself is strongly associated with androgenetic alopecia (male hair loss) (5). XEDAR is widely expressed, notably in embryonic basal epidermal cells and maturing hair follicles (3, 6, 7). Even though it does not contain a cytoplasmic death domain, XEDAR can associate with Fas and induce EDA‑A2 dependent apoptosis (6, 8). Its transcription is directly induced by p53, and XEDAR mediated cell death is p53 dependent (6, 9). XEDAR is down‑regulated in breast, colon, and lung cancers, particularly in cases with p53 mutations (6, 10). XEDAR also plays a role in EDA‑A2 induced skeletal muscle degeneration and osteoblast differentiation (7, 11).