Esophagin, also known as small proline-rich protein 3 (SPR3) or Cornifin ∫, belongs to the cornifin family of cornified-envelope structural proteins. It is expressed in mucosal epithelia such as esophagus and tongue and is strongly induced during epidermal keratinocyte differentiation. Due to its highly inducible nature, Esophagin is considered a marker of squamous differentiation. Esophagin serves as a cross-linking protein within the cornified cell envelope and may play a role in the maintenance of normal esophageal epithelial homeostasis. It shares significant homology with the related proteins, SPRR1 and SPRR2. Esophagin is typically not expressed in healthy human epithelium, but its expression is upregulated in numerous hyperproliferative disorders of the skin. Contrastly, its expression is dramatically downregulated in esophageal squamous cell carcinoma.