Fizzy-related protein, known as fzr, is a conserved eukaryotic gene that has been recently identified as a 7WD domain family member and is implicated in cell cycle regulation of Drosophila and yeast. Retroviral overexpression of fzr in B-lymphoma cells reduces tumor formation. Fzr overexpression increases B-lymphoma cell susceptibility to natural killer cell (NK) cytotoxicity. Fzr has been implicated in a new category of genes which suppress B-cell tumorigenesis. Current research suggests a novel role for fzr in the target cell interaction with NK cells. Fzr also negatively regulates the levels of cyclins A, B and B3. Loss of fzr causes progression through an extra division cycle in the epidermis and inhibition of endoreduplication in the salivary gland, in addition to failure of cyclin removal. Conversely, premature fzr overexpression downregulates mitotic cyclins, inhibits mitosis and transforms mitotic cycles into endoreduplication cycles.