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All terrestrial plants possess stomata, which are located on the epidermal surface and comprise a pore surrounded by a pair of guard cells. Unique signal transduction mechanisms operate in the guard cells to regulate stomatal opening and closing in response to various intrinsic and extrinsic factors. However, some aspects of guard cell signaling remain unclear. Here, Oh et al. have employed a chemical biology approach to identify a novel stomatal opening chemical, PP242. They show that PP242 strongly inhibits early signal transduction of abscisic acid, which induces stomatal closure. As part of this pathway, they identified B3 clade Raf-like kinases as targets of PP242. These findings deepen our understanding of the crosstalk between signaling pathways operating to regulate stomatal movement.