Of the approximately 200 proteins that have been identified for the vaccinia virus (VACV) genome, many are currently listed as having an unknown function, and seven of these are also found in all other poxvirus genomes that have been sequenced. The G5R protein of VACV is included in this list, and to date, very little is known about this essential and highly conserved protein. Conventional similarity searches of protein databases do not identify significantly similar proteins, and experimental approaches have been unsuccessful at determining protein function.