At the late stage of PC in patients below 55 years of age, similarly to early and then late PC in 60–70-year-olds, we observed heightening of Notch activity through triggering the expression of additional ligands (DLL4, JAG2, DLK1), Notch receptors, TFs (HES4, HES5, HEY2, HEYL, PTCRA), and intensified cross-talk with the Wnt pathway through DVLs (DVL1, DVL2) until its activity extinction in elderly men, especially at the late stage of PC. Here, HES4 is linked to pachyonychia congenita.