GREMLIN 2 (GREM2)—formerly, protein related to Dan and cerberus (PRDC)—is a potent antagonist of the bone morphogenetic proteins 2 and 4, but little else in known about its functions. We found that Grem2^-/- mice developed small deformed mandibular and maxillary incisors, indicating that GREMLIN2 is required for normal tooth morphogenesis. Although DEXA scans suggested that bone mineral density might be increased in Grem2^-/- mice, histology did not reveal any evident bone phenotype. Grem2^-/- mice did not display any other notable phenotypes evaluated in a high-throughput screening process that encompassed a range of immunologic, metabolic, ophthalmic, and behavioral parameters. Our findings indicate that Grem2 can be added to the growing list of genes that affect tooth development in mice.