However, the underlying molecular mechanisms are different: in the Grhl3 conditional knockout epidermis, there is a reduction in the level of tumor suppressor phosphatase and tensin homolog (PTEN), a direct target of GRHL3 regulation, which triggers dysregulation of the PI3K/AKT/mTOR signaling pathway [5]; in the Grhl1−/− mice, the underlying molecular mechanism involves aberrant keratinocyte terminal differentiation and subacute skin barrier defects which, by inducing tumor-promoting mild chronic inflammatory microenvironment in the skin, increase the risk of skin cancer [9, 10]. Here, GRHL3 is linked to neoplasm.