Dental follicles are involved in odontogenesis, periodontogenesis, and tooth eruption. Dental follicles are unique structures, considering that their remnants can persist within the jawbones after odontogenesis throughout life if the tooth does not erupt. Pathological changes may occur in these tissues as individuals age. The changes range from benign to life threatening. Thus, the assessment of age‐related changes in dental follicles associated with unerupted teeth is of paramount importance. In this review, we summarize the physiological roles and changes in dental follicles in odontogenesis, tooth eruption, and aging, in addition to the pathological changes associated with these structures. We encourage investigators to consider this peculiar tissue as a unique model and explore its potential to clarify its importance from the viewpoints of developmental biology, tissue physiology, and pathology.

Next‐generation sequencing has revealed mutations in several bone‐related lesions and was recently used to uncover the genetic basis of giant cell lesions of the jaws (GCLJ). Consistent with their benign nature, GCLJ show a low tumor mutation burden. They also harbor somatic, heterozygous, mutually exclusive mutations in TRPV4, KRAS, or FGFR1. These signature mutations occur only in a subset of lesional cells, suggesting the existence of a ‘landscaping effect’, with mutant cells inducing abnormal accumulation of non‐mutant cells that form the tumor mass. Osteoclast‐rich lesions with histological similarities to GCLJ can occur in the jaws sporadically or in association with genetically inherited syndromes. Based on recent results, the pathogenesis of a subgroup of sporadic GCLJ seems closely related to non‐ossifying fibroma of long bones, with both lesions sharing MAPK pathway‐activating mutations. In this review, we extrapolate from these recent findings to contextualize GCLJ genetics and we highlight the therapeutic implications of this new information. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.