NOTCH2 and pachyonychia congenita: In line with the above, we revealed an increase in Notch signaling activity among patients under 55 years of age that intensified with more advanced-stage PC involving the most essential Notch members, such as receptors (NOTCH2-4), ligands (JAG2, DLL4), and HEYL, a Notch-specific TF (Figure 1).