AbstractWe observed that Lgr4K5 KO mice had sparse head hair and focal alopecia behind their ears, as observed in tabby (Eda) and downless (Edar) mice, which are models of the human genetic disorder hypohidrotic (anhidrotic) ectodermal dysplasia (HED). Lgr4‐deficient mice showed partial impairment in hair follicle development with reduced expression of Edar, Lef1, and Shh, which were essential for hair follicle morphogenesis, in the epidermis. Immunohistochemical analysis of Lgr4−/− mice epidermis using shh antibody showed reduced numbers of hair placodes, and we also detected higher phosphorylation of Smad1/5/8, which is required to suppress normal hair follicle induction. We suspected that Lgr4 might be a novel gene class regulating the development of hair follicles. Developmental Dynamics 237:2235–2242, 2008. © 2008 Wiley‐Liss, Inc.