Cell surface integrin receptors mediate cell adhesion, migration and cellular signaling in all nucleated cells. They are activated by binding to extracellular ligands or by intracellular proteins, such as kindlins that engage with their cytoplasmic tails. Cells in the periodontal tissues express several integrins with overlapping ligand-binding capabilities. A distinct phenotype in the periodontium has only been described for knockouts or mutations of three integrin subunits, alpha 11, beta 6 and beta 2. Integrin alpha 11 beta 1 appears to have some regulatory function in the periodontal ligament of continuously erupting incisors in mice. Integrin alpha v beta 6 is expressed in the junctional epithelium (JE) of the gingiva. Animals deficient in this receptor develop classical signs of periodontal disease, including inflammation, apical migration of the JE and bone loss, suggesting that it plays a role in the regulation of periodontal inflmmation, likely through activation of transforming growth factor-beta 1. Lack of integrin activation in the JE is also associated with periodontitis. Patients with kindlin-1 mutations have severe early-onset periodontal disease. Finally, patients with mutations in the leukocyte-specific beta 2 integrin subunit have severe periodontal problems due to lack of transiting neutrophils in the periodontal tissues. (C) 2014 Elsevier Inc. All rights reserved.