The stratum corneum of the epidermis is composed of stacked dead corneocytes embedded in lipid layers and is the main protective shield of the skin. The thickness of the stratum corneum is maintained fairly constantly through the balance between new cell creation and old cell removal. Corneodesmosomes are the main intercellular adhesive structures in the stratum corneum. They are transformed from desmosomes at the most superficial layer of the stratum granulosum of the epidermis. The major compositional distinction from desmosomes is the presence of corneodesmosin in the extracellular portion. Furthermore, corneodesmosomes are structurally different from desmosomes in that (1) they do not have a tri-lamellar desmoglea but rather one that is homogeneously electron-dense and (2) attachment plaques are integrated into a part of the cornified cell envelopes. When the extracellular regions of corneodesmosomes are fully degraded, desquamation occurs. The degradation process of corneodesmosomes is carefully controlled by a number of proteases and their inhibitors. The most important proteases involved in this process are the kallikrein-related peptidases. Their main inhibitor is the lympho-epithelial Kazal-type related inhibitor. Other regulators of this process include matriptase, meprin and mesotrypsin.