The keystone event in CeD pathogenesis is the activation of a gluten-specific immune response that is driven by molecular interactions between gluten-derived peptides, as the indispensable environmental factor, the HLA-DQ2/8 locus, as the main predisposing genetic factor, and the enzyme transglutaminase 2 (tTG2), the identified CeD-specific autoantigen. The gene discussed is TGM2; the disease is cranioectodermal dysplasia.