Go in! Go out! Inducible control of nuclear localization

•Protein localization regulates function.•Gene expression is controlled by nuclear localization of transcriptional regulators.•The basic signals dictating nuclear import and export have been deciphered.•Small molecules can be used to control nuclear transport of engineered proteins.•Light-activatable proteins can provide reversible control of nuclear localization. Cells have evolved a variety of mechanisms to regulate the enormous complexity of processes taking place inside them. One mechanism consists in tightly controlling the localization of macromolecules, keeping them away from their place of action until needed. Since a large fraction of the cellular response to external stimuli is mediated by gene expression, it is not surprising that transcriptional regulators are often subject to stimulus-induced nuclear import or export. Here we review recent methods in chemical biology and optogenetics for controlling the nuclear localization of proteins of interest inside living cells. These methods allow researchers to regulate protein activity with exquisite spatiotemporal control, and open up new possibilities for studying the roles of proteins in a broad array of cellular processes and biological functions.