Despite the fact that the genomic presence of gN/UL49.5 is highly conserved in herpesviruses, the protein shows significant amino-acid sequence as well as functional variation.. The experimental structure of HSV-1-encoded UL49.5 protein has been largely unknown. Up to date, only the experimental structure of the TAP-inhibiting UL49.5 protein of varicellovirus BoHV-1 has been revealed . It has been shown thatBoHV-1-encoded UL49.5 protein is a prototypic varicelloviral TAP inhibitor with the broadest activity. The inhibition process depends on the ability to block structural rearrangements within the TAP complex, presumably leading to the ER-associated degradation (ERAD) system to recognize the misfolded TAP and directing UL49.5 and TAP for proteasomal degradation . Despite huge similarities within alfaherpesvirus subfamily many differences on the molecular level have been reported. Therefore, it is crucial to determine whether the molecular, structural, and functional features of HSV-1-encoded UL49.5 are similar or show differences to other homologs of gN/UL49.5 proteins from other herpesviruses.