Interferon epsilon (IFNe) is a unique member of the type I IFN family of cytokines which has evolved distinct features that enable it to protect mucosal tissues from disease.  We have demonstrated that it is critical for optimal protection of the female reproductive tract (FRT), where it is constitutively expressed, from bacterial and viral infection. This action involves activation of direct antiviral and antibacterial activity on parenchymal cells of these organs as well as regulating immune cell recruitment and activation. A remarkable, unique feature of IFNe is the location and regulation of expression. The constitutive epithelial cell expression in the FRT is regulated by ETS factors (e.g. Elf 3), its physiological fluctuations are influenced by hormones; but unlike conventional type I IFNs α and β, it is not pathogen inducible. We show that these features have important implications for immunoregulation and disease pathogenesis.   While IFNe acts through common type I receptor chains IFNAR1 and IFNAR2 and activates canonical JAK/STAT signaling, its distinct receptor chain interactions provide IFNe with a novel repertoire of immune functions. These properties are not only operative in infectious and inflammatory diseases, but also in controlling tumourigenesis.  We have recently shown IFNe is normally expressed that the cell of origin of high grade serous ovarian cancer (HGSOC), but expression is reduced in these tumours consistent with an anti-tumour cytokine. Indeed, using murine models, we demonstrate that endogenous and exogenous IFNe is a potent inhibitor of ovarian tumour development and particularly of peritoneal metastasis where it may have therapeutic potential.