HE4 (also WDFC2; WAP Four-disulfide core domain protein 2) is a secreted, 25kD glycoprotein member of the Whey Acidic Protein family of molecules. It is expressed by a wide variety of epithelial cells, including respiratory epithelium, salivary gland mucous cells, breast duct epithelium, distal tubule renal epithelium, and epididymal epithelium. It is believed to play a role in innate defense, and/or function as a protease inhibitor (perhaps for neutrophil elastase). Although ovarian cuboidal epithelium does not express HE4, ovarian epithelial tumors do, leading to the suggestion that HE4 could represent a tumor marker for ovarian cancer. Mature human HE4 is 94aa in length. It contains two WAP domains that likely mediate antiprotease and/or antimicrobial activity (aa31-73 and 74-123). There are four potential splice variants. One shows a deletion of aa27-74, while three others show aa substitutions: 28aa for aa75-124, 23aa for aa1-74, and 10aa for aa71-124. Over aa31-124, human HE4 shares 63% aa identity with an extended (144 aa) mouse form of mature HE4.