ERV3-1 is an endogenous retroviral envelope gene located on chromosome 7 that encodes a transmembrane protein functioning as a syncytin family member. 1 The ERV3-1 protein contains a transmembrane domain anchoring the envelope heterodimer to viral membranes and a fusion peptide mediating membrane fusion between viral and target cell membranes. 1 While ERV3-1 expression occurs throughout placental development in trophoblast tissue alongside major syncytin genes ERVW-1 and ERVFRD-1, its specific fusogenic contribution remains understudied. 1 ERV3-1 exhibits altered expression in multiple disease contexts. In acute myelogenous leukemia, ERV3-1 shows elevated expression in patient leukocytes, particularly in myeloid lineage cells, with protein localization at leukemic cell membranes. 2 In myelodysplastic syndrome, ERV3-1 upregulation correlates with dyserythropoiesis and activates the TLR3-IRF inflammatory axis linked to bone marrow failure pathogenesis. 3 Conversely, in breast cancer, ERV3-1 demonstrates tumor suppressor function with significantly lower expression in advanced stages, showing strong diagnostic performance (AUC: 0.819). 4 In colon cancer, ERV3-1 knockout reduces cellular invasion, migration, and in vivo tumor growth. 5 Additionally, the rs67047829 polymorphism introducing a premature termination codon in ERV3-1 associates with lower body mass index in Polish populations. 6 These divergent roles suggest ERV3-1 functions context-dependently in both placental fusion and cancer biology.