Human endogenous retroviruses (HERVs) are residues of exogenous retroviruses which have integrated into the human genome millions of years ago, accounting for about 8%-12% of the whole genome. Most HERVs don’t have an intact open reading frame due to mutations, deletions, etc. However, some HERVs can encode viral proteins, for example, Human endogenous retrovirus W(HERV-W), a member of the gamma retrovirus-like family isolated from patients with multiple sclerosis. Syncytin-1, encoded by HERV-W, plays a role in cell fusion and immunoregulation during human placental development. Under physiological conditions, the transcriptional activity of HERV-W is inhibited by epigenetic regulation, for example, hypermethylation, which can be activated by environmental factors such as drugs, radiations and viral infections as well as genetic factors. Several studies found abnormal expression of HERV-W in patients with some cancers, mental illnesses, and autoimmune diseases. Therefore HERV-W may play an important role as “bridge” and “trigger” in the development of diseases. Currently the monoclonal antibody GNbAC1 targeting Syncytin-1 has been used in clinical research of multiple sclerosis, which also has a good application prospect for type 1 diabetes. Further research on HERV-W might provide a valuable way for diagnosis and treatment of certain diseases.