The replication and stable maintenance of latent Epstein-Barr virus DNA episomes in human cells requires only one viral protein, Epstein-Barr nuclear antigen 1 (EBNA1). EBNA1 binding protein 2, also designated p40/EBP2, is a nuclear protein required for the processing of the 27S pre-rRNA. EBP2 is highly conserved across species and is ubiquitously expressed in human tissues, especially myelogenous leukemia K-562. EBP2 specifically interacts with EBNA1, supporting the long-term maintenance of Epstein-Barr virus plasmids in human cells. The EBNA1-EBP2 complex is important for the stable segregation of Epstein-Barr virus episomes during cell division.