Autophagy is an important process by which cells remove and degrade aging, unnecessary, or damaged components. It is critical for development and the maintenance of overall health. In selective autophagy, the cell targets specific cellular components for degradation by attaching a tag, such as the protein ubiquitin. Removal of the tagged proteins then occurs through the combined efforts of a large number of other proteins that guide it to a specialized vesicle, the phagophore. Important players in this process are LC3, a protein that aids in selective recruitment of tagged components, and SQSTM1, a tagged cargo receptor. Selective autophagy requires that these two proteins interact with each other in multiple aggregated forms, and their interaction has been widely studied. However, we still do not fully understand the way that the proteins associate in intact cells. Now Basic Sciences investigator Anne Kenworthy and her laboratory use state-of-the-art fluorescence microscopy techniques (commonly referred to as FRET and FRAP) to directly visualize the interaction of SQSTM1 and LC3 in living cells. They show that SQSTM1 is present in large aggregates in the cytoplasm of cells, and that association with these aggregates diverts LC3 from the nucleus to the cytoplasm. Their work also defines functions for specific regions of SQSTM1 that were not previously appreciated and establishes the foundation for a straightforward assay to monitor the aggregation of soluble proteins in intact cells. The work is published in the journal Autophagy [L.J. Kraft, et al. (2016), Autophagy, 12, 1660].