INTRODUCTION: Endometriosis is an estrogen-dependent, chronic, pro-inflammatory disease that develops in 6-10% of women of reproductive age. Symptoms include chronic pelvic pain, dysmenorrhea and subfertility. Recently, VEZT was identified as an endometriosis risk gene that was upregulated during the secretory phase of the menstrual cycle1. VEZT encodes for an adherens junction protein vezatin and to date, the function of VEZT in human endometrium is unknown. METHODS: Immunohistochemistry was used to determine VEZT protein (vezatin) expression and localisation in a tissue microarray of eutopic endometrium. Cellular localisation of vezatin was further evaluated using immunofluorescence double staining of endometriosis ectopic lesions and eutopic endometrium compared to non-endometriosis eutopic endometrium. To demonstrate VEZT regulation by secretory phase hormones, immortalised endometriosis endometrial stromal cells and a non-endometriosis endometrial stromal cell line were treated with estradiol-17β, medroxyprogesterone acetate and cAMP to induce decidualisation and quantify VEZT mRNA by qPCR. RNASeq was then used on immortalised endometriosis endometrial stromal cells and a non-endometriosis endometrial stromal cell line that were transfected to over express VEZT. Ingenuity Pathway Analysis (IPA) was then performed on the top 500 up and down regulated genes to determine pathways significantly influenced by VEZT overexpression. RESULTS: Vezatin was localised to glandular epithelium, decidualised stromal cells, endothelium and leucocytes in secretory phase eutopic endometrium as well as CD10+stromal cells, epithelium and CD45+leucocytes in ectopic lesions. Vezatin also colocalised with CD31, CD56 and CD68+cells. Following decidualisation, VEZT mRNA expression was increased 2-fold compared to non-decidualised stromal cells and the most upregulated pathway by the overexpression of VEZT in stromal cells was the interferon pathway. CONCLUSION: VEZT/vezatin expression in decidualised stromal cells, endothelium and leucocytes indicates a functional role in mesenchymal-epithelial transition, angiogenesis and inflammation. VEZT may therefore modulate these processes in conjunction with interferon signalling and significantly contribute to the pathogenesis of endometriosis.