Fig. 1.

Schematic of the layers of the epidermis and phases of functional cell death, corneoptosis. Epidermal cells differentiate vertically through the stratified layers of the epidermis, the SB, SS, SG, and SC. The SG is made up of three layers, SG3, SG2, and SG1, with SG1 cells undergoing functional cell death, corneoptosis. In phase I of this process, there is sustained high [Ca²⁺]_i at neutral pH for about 60 min, which may activate transglutaminases (TGases). In phase II, the high [Ca²⁺]_i is sustained, and pH becomes acidic, which may activate DNases (DNase1L1 and DNase2) and SASPase. KHGs are eliminated, and nuclear DNA is completely degraded, completing the cell death process leading to a functional corneocyte. Corneocytes mature within the SC and are finally shed off in a process called desquamation. Adapted with permission from ref. 6.