Post-translational modification of proteins, such as phosphorylation, ubiquitination, and SUMO modification, is an important means of regulating a variety of cellular activities. SUMOs (Small Ubiquitin related Modifiers) are covalently conjugated to lysine residues of many proteins by a mechanism that parallels ubiquitination (1). The effects of sumoylation, however, are distinct from ubiquitination. Sumoyla-tion does not directly control protein stability, but regulates proteins through various mechanisms that include modulation of protein-protein interactions, protein-nucleic acid interactions, subcellular protein localization, and enzymatic activity (1-4). There are many examples, however, where the molecular bases for the effects of sumoylation on protein function and on cellular processes remain unclear. Here, we outline the use of an inducible and reversible sumoylation system, based on rapamycin heterodimeriza-tion, as a novel tool to characterize the functions of sumoylation in mammalian cells.