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Precise regulation of the NFAT (nuclear factor of activated T cells) family of transcription factors (NFAT1–4) is essential for vertebrate development and function 1. In resting cells, NFAT proteins are heavily phosphorylated and reside in the cytoplasm; in cells exposed to stimuli that raise intracellular free Ca 2+ levels, they are dephosphorylated by the calmodulin-dependent phosphatase calcineurin and translocate to the nucleus 1. NFAT dephosphorylation by calcineurin is countered by distinct NFAT kinases, among them casein kinase 1 (CK1) and glycogen synthase kinase 3 (GSK3) 1, 2, 3, 4, 5. Here we have used a genome-wide RNA interference (RNAi) screen in Drosophila 6, 7 to identify additional regulators of the signalling pathway leading from Ca 2+–calcineurin to NFAT. This screen was successful because the pathways regulating NFAT subcellular localization (Ca 2+ influx, Ca 2+–calmodulin–calcineurin …