We describe the isolation and characterization of a novel cDNA encoding a polypeptide that interacts in a yeast two-hybrid system as well as in mammalian cells with the retinoblastoma (RB) protein. This new protein, which we call Rim, consists of 897 amino acids, has two leucine zipper motifs, and has a LECEE sequence previously identified as an RB-binding domain. Rim also has an E1A/CtBP-binding motif and four putative nuclear localization signals. Rim mRNA is expressed ubiquitously at low levels in all human adult tissues tested and at much higher levels in several tumor cell lines. The Rim gene (HGMW-approved symbol RBBP8) is localized on human chromosome 18q11.2.