Ceramides are indispensable constituents of the stratum corneum (SC), the uppermost impermeable layer of human skin. Ceramides with shorter (4 to 8 carbons long acyl chains) fatty acid chains increase skin and model membrane permeability, while further shortening of the chain leads to increased resistance to penetration almost as good as in ceramides from healthy skin (24 carbons long on average). Here we addressed a question to what extent the atomistic CHARMM36 and coarse-grain MARTINI molecular dynamics (MD) simulations reflect the skin permeability data . As a result, we observed the same bell-shaped permeability trend for water as was observed in the skin and multilayer membrane experiments for model compounds. We showed that the enhanced permeability of the short ceramides is mainly caused by the disturbance of their head group conformation due to their inability to accommodate the shorter lipid acyl chain into a typical hairpin conformation, which further lead to their destabilization and phase separation. As MD simulations described well delicate structural features of SC membranes, they seem to be suitable for further studies of the SC superstructure including the development of skin penetration enhancers for transdermal drug delivery and skin toxicity risk assessment studies.