Human epididymis secretory protein E4 （HE4）is a protein in humans that is encoded by the WFDC2 gene.This gene encodes a protein that is a member of the WFDC domain family. The WFDC domain contains eight cysteines forming four disulfide bonds at the core of the protein, and functions as a protease inhibitor in many family members. This gene is expressed in pulmonary epithelial cells, and was also found to be expressed in some ovarian cancers.

HE4 is a serum biomarker to aid in differentiating benign and malignant disease in women with a pelvic mass.Serum HE4 levels are relatively stable across the menstrual cycle of reproductive aged women and can be determined on any day to evaluate risk of ovarian malignancy.

HE4 is a tumor marker of ovarian cancer.It has important clinical significance in the early diagnosis, monitoring and prognosis evaluation of treatment, also brings more powerful basis for early ovarian cancer detection.