Particularly, nectin-1 and nectin-4 trans-interactions regulate the reformation of the actin cytoskeleton through the activation of Rac1, a member of the Rho family of small GTPases that enhances the clustering of adhesion molecules.12, 15 Defective trans-dimerization due to loss or impairment of either Nectin-1 (also known as PVRL1) or Nectin-4 causes a defect in normal cell-cell adhesion and causes Cleft Lip/Palate ED (CLPED1) and EDSS1 respectively4, 16, 17 both characterized by abnormalities in hair and teeth along with cutaneous syndactyly. Here, RAC1 is linked to ectodermal dysplasia-syndactyly syndrome.