Lipase M Is Essential for Skin Barrier Function in Mice

A functional skin barrier is essential for restricting water losses for terrestrial animals. The outermost layer of this barrier, the stratum corneum, consists of corneocytes (derived from terminally differentiated keratinocytes) coated with a protein‐rich envelope and a conjugated lipid‐rich envelope embedded in an organised hydrophobic intercellular lipid matrix. Gene mutations and environmental insults that affect corneocyte formation or the intercellular lipid matrix organisation cause skin barrier defects in mice and humans. Here we demonstrate mice homozygous for a loss‐of‐function mutation in the Lipm gene exhibit a diminished and discontinuous intercellular lipid matrix and a profound skin barrier defect associated with neonatal lethality. These findings suggest the protein encoded by the Lipm gene, lipase M (LIPM), is essential for skin barrier function by impacting intercellular lipid matrix organisation in the stratum corneum.