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A variety of enzymes in the plant cell wall are regulated by secretion of specifically acting protein inhibitors. Members of the invertase/pectin methylesterase inhibitory (CIF/PMEI) family target two different enzymes: invertases or pectin methylesterases. On pages 3437-3447, Hothorn et al. give insight into how such target specificity is implemented on homologous structures. The crystal structure and biochemical analysis of a PMEI along with protein engineering approaches revealed a mobile and functionally critical helical hairpin that in the invertase-specific inhibitor CIF is observed only in a closed conformation. In the PMEI structure, the mobile hairpin mediates target specificity towards plant pectin methylesterase, whereas invertase-specific inhibitors like CIF employ their four-helix core to act specifically on plant acid invertases. The cover artwork (by M. Hothorn) shows a representation of the PMEI structure. Arrows point from the helical hairpin to a corresponding target pectin methylesterase (left) and from the four-helix core to a corresponding target invertase (right).