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Agrobacterium species transfer single-strand DNA and virulence effector proteins to plants. To understand how Agrobacterium achieves interkingdom horizontal gene transfer, scientists have investigated how the interaction of bacterial effector proteins with host proteins directs T-DNA to the plant nucleus. VirE2, a single-strand DNA binding protein, likely plays a key role in T-DNA nuclear targeting. However, subcellular trafficking of VirE2 remains controversial, with reports of both cytoplasmic and nuclear localization. The recent discovery that phosphorylation of the VirE2 interacting protein VIP1 modulates both nuclear targeting and transformation may provide a solution to this conundrum. Novel experimental systems that allow tracking of VirE2 as it exits Agrobacterium and enters the plant cell will also aid in understanding virulence protein/T-DNA cytoplasmic trafficking.