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Previous reports have suggested that this protein regulates glucose metabolism and inflammation. In the present study, to analyze the involvement of RELM\u2010\u03b2\/FIZZ2 in tooth development, we immunohistochemically examined the localization of RELM\u2010\u03b2\/FIZZ2 in tooth germs of embryonic days (E) 15\u201020 and postnatal days (P) 7\u201042 rats. RELM\u2010\u03b2\/FIZZ2 was hardly detected in the tooth germ at the bud (E15) stage. However, at the cap (E17) and bell (E20) stages, this protein was detectable in the inner enamel epithelium; whereas cells in the other parts of the enamel organ including the outer enamel epithelium and stellate reticulum did not show the immunoreactivity. During the root formation stage (P14\u201028), cells in Hertwig's epithelial root sheath (HERS) localized RELM\u2010\u03b2\/FIZZ2. Intense immunoreactivity was also seen in the matrix of the root dentin facing the HERS and the dental follicle. This reactivity was not present on the more upwardly located dentin surface. In contrast, cementum matrix positive for osteopontin and bone sialoprotein was observed on the dentin instead of immunoreactivity for RELM\u2010\u03b2\/FIZZ2. Osterix\u2010positive cells, indicating cementoblast progenitors, were also detected in the dental follicle near the matrix positive for RELM\u2010\u03b2\/FIZZ2. These results suggest that RELM\u2010\u03b2\/FIZZ2 secreted by the inner enamel epithelium was mainly localized in the matrix at the surface of the apical root dentin and might be involved in cementogenesis. Anat Rec, 2017. \u00a9 2017 Wiley Periodicals, Inc. 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