Human papillomavirus type 16 (HPV-16) E5 protein, along with the more publicized E6 and E7 proteins of this virus, has been found to be oncogenic. E5 is a highly hydrophobic membrane-bound protein of 83 amino acids associated with the Golgi apparatus, endoplasmic reticulum, and nuclear membrane in infected cells. E5 can activate epidermal growth factor receptor (EGFR) through binding to the 16 kD subunit of protein pump ATPase leading to a reduced downregulation of EGFR receptors. The activation of EGFR can initiate biochemical cascades that lead to overexpression of a variety of protooncogenes and stimulate rapid cell growth. Moreover, E5 can inhibit the expression of tumor suppressor gene p21((WafI/SdiI/CipI)) and impair the control of cell cycle checkpoint. E5 protein has been identified as a potential tumor vaccine target antigen.