In an attempt to understand the role of genes with no known function, in the protozoan parasite Entamoeba histolytica, an analysis of the proteome was carried out and a Lysine-Rich protein (KRP) was identified for further study. This protein has a modular structure with four domains and was found to be expressed and localized to the cell surface of E. histolytica trophozoites. The KRP over expressing cells were 80% less virulent as compared to the cells under expressing the gene as determined by the ability of the cells to kill in vitro target cells. The results suggest that KRP may have a role in the cytopathogenesis of the parasite