Members of the Herpesviridae family represent the most complex human pathoghens, with an icosahedral capsid surrounded by a multiprotein tegument layer and a cell-derived, glycoprotein-enriched lipid layer. Among that, glycoprotein N (gN/UL49.5 protein) is conserved throughout the herpesvirus family . gN is a type I transmembrane protein with a single transmembrane-spanning domain. The preferred model predicts a topology in which the larger N-terminal domain is positioned toward the lumen of endoplasmic reticulum (ER), while the C-terminal fragment is oriented toward the cytosol . In the presence of glycoprotein M (gM) gN/UL49.5 is translocated to the trans-Golgi network (TGN). The interaction with the N-terminal core of gM, which consists of eight transmembrane domains, is required for UL49.5 to be released from the ER.