Dengue virus (DENV) is a single-stranded positive-sense RNA virus that causes dengue fever, belonging to the Flaviviridae family. A total of four antigenically distinct serotypes (DENV1, DENV2, DENV3 and DENV4) have been identified with different manifestations of clinical symptoms despite sharing 65% similarities. DENV non-structural protein 1 (NS1), one of the 7 non-structural proteins in DENV, is a highly conserved 48-kDa glycoprotein with serotype-specific epitopes that enable differentiation of DENV serotypes. NS1 is the only protein that is continuously secreted by infected host cells. NS1 is secreted in a hexamer form, which is composed of three dimers with a detergent-sensitive hydrophobic central cavity that carries a cargo of ~70 lipid molecules. The NS1 can be detected in the serum of patients from the onset of symptoms, which serves as a more useful diagnostic marker for the early detection of DENV. Furthermore, DENV NS1 plays a pathogenic role in vascular leakage.