RETINOBLASTOMA-RELATED (RBR) is the plant homolog of the metazoan Retinoblastoma protein (pRB) tumor suppressor and is a conserved cell cycle regulator. RBR has been linked to several multicellularity-related processes, such as controlled cell proliferation, stem cell regulation, and asymmetric cell division. These RBR activities are achieved via protein-protein interactions; however, it is not clear how these interactions and functions have diversified throughout evolution. Recently, J. León Ruiz and A. Cruz-Ramirez identified the potential RBR protein interactions in plant lineages with different morphologies, physiologies, and developmental processes. First, the authors detected high conservation in the RBR proteins at the structural level, for instance, in the LxCxE-cleft, which is responsible for mediating protein interactions; however, other features, such as phosphorylation sites, are not similar in some RBR orthologues. To find the potential RBR interactors, the authors searched for LxCxE-containing proteins in the genome of 29 representative species. A gene ontology classification revealed that most LxCxE-containing proteins are associated with chromatin regulation at different levels. Interestingly, other potential RBR-LxCxE associations were detected with transcriptional regulators, but they were mostly species- or clade-specific. This work provides a valuable resource for the characterization of novel RBR functions in different clades, including some emerging evo-devo models such as Physcomitrium patens, Marchantia polymorpha, and Ceratopteris richardii. (Summary by Humberto Herrera-Ubaldo @herrera_h) Plant J. 10.1111/tpj.16012