Cleft Lip/Palate-Ectodermal Dysplasia and Ectodermal Dysplasia-Syndactyly Syndrome are rare congenital disorders caused by recessive mutations in the PVRL1 and PVRL4 genes, respectively. These genes encode nectins 1 and 4, an emerging class of molecules acting in cooperation with cadherins to form cell-cell adhesion especially at adherens junctions. Their role in skin, hair and teeth biology and in the fine-tuning morphogenesis of craniofacial (lip/palate) and limbs is yet to be outlined prompting future research. We propose refer to these entities (nectin 1-ED and nectin 4-ED) as "nectinopathies", which are likely to be underestimated/underdiagnosed ED syndomes.