Atopic dermatitis (AD) and psoriasis share a distinct genetic linkage to the epidermal differentiation complex (EDC) locus at lq21. Semidominant mutation in the filaggrin (FLG) gene associated with AD and a copy number variation within the late cornified envelope (LCE) genes associated with psoriasis provide compelling evidence for their role in the pathophysiology of these conditions. A computational approach to identify conserved noncoding elements (CNEs) in the EDC queried for regulatory functions. Across a wide range of mammalian genomes, a high degree of synteny and linearity suggested an evolutionary conserved regulatory function in the EDC. CNEs could exhibit enhancer or repressor activity in differentiating or proliferating conditions. EDC gene expression could be ...