Since the first discovery [12], over 50 mutations that include frameshift, nonsense, missense, and splice-site mutations have been identified on the genes encoding PS/γ-secretase components (i.e., PS1, Pen2, and Nicastrin), resulting in familial Acne inversa/hidradenitis suppurativa (HS)—a chronic and recurrent inflammatory skin disease [13]. Here, PSENEN is linked to inflammatory skin disease.