Cystatin E/M, also known as Cystatin 6 or Cystatin M, is a protein encoded by the CST6 gene in humans . It belongs to the type 2 cystatin family. The cystatin superfamily is a well-established group of cysteine protease inhibitors, which are proteins that block the activity of certain enzymes that break down other proteins . Within this superfamily, type 2 cystatins, including Cystatin E/M, are typically extracellular proteins found in various body fluids and secretions. One of the most critical roles of Cystatin E/M is in the formation and maintenance of the skin barrier. It regulates a specific proteolytic pathway essential for epidermal cornification (the formation of the outer skin layer) and hair follicle morphogenesis.