FMRP is an RNA binding protein whose absence produces pathological manifestations of the fragile-X syndrome. FMRP is a component of mRNP complexes found in association with actively translating polyribosomes, RNA complexes trafficking in neurites, RNA granules in cytoplasm and, in Drosophila, with the RNAi machinery. We report here the identification and characterization of a novel FMRP-interacting protein associated to polyribosomes as a component of mRNP complexes containing FMRP. We named this protein 82-FIP (82-kD FMRP Interacting Protein). FMRP interacts with 82-FIP through a novel interaction motif located in its N-terminal region. The distribution of 82-FIP in different areas of the brain is very similar to that of FMRP. However, unlike FMRP, 82-FIP is found in both nucleus and cytoplasm in some neurons, while it appears only cytoplasmic in others. Subcellular distribution of 82-FIP is cell cycle-dependent in cultured cells, suggesting that the composition of some FMRP-containing RNP complexes may be cell cycle-modulated.