The Arabidosis dehydrin Rab18 is expressed in response to drought and the phytohormone ABA. As a clue to a general dehydrin function, some dehydrins are found to interact in an orderly manner with negatively-charged lipids, supporting the idea of a key role in safeguarding membrane integrity. Interaction between dehydrins and membranes studied so far has been driven by general electrostatic attractions. Here, we report on specific binding of Rab18 with inositol lipids, especially PI(4,5)P2. This binding is not purely under the control of global protein electrostatics since Rab18 fails to bind to lipid vesicles with a high negative net charge (DOPC:DOPG, 3:1). Instead, Rab18 binds strongly to inositol lipids even at low negative vesicle net charge (i.e. DOPC:DOPI(4,5)P2, 98:2). Further, Rab18 show a high specificity to inositol lipids with a phosphate in the 5th position on the inositol ring i.e. PI(5)P and PI(4,5)P2 whereas a phosphate at 3rd position restrains Rab18 binding (i.e. PI(4,5)P2>PI(3,5)P2>PI(3,4)P2 and PI(5)P>> PI(3)P). Moreover, Rab18 specificity to inositol lipids is mainly augmented by the Arg in the protein sequence and when all six Arg are replaced by Lys is the binding of Rab18 to PI(4,5)P2 almost abolished. The two Arg preceding the first K-seg (Rab18Arg125-126) are key residues in binding PI(4,5)P2 and the mechanistic implication of these Arg is elucidated. We put forward the idea that Rab18 is a conditional peripheral membrane protein that sense and respond to lipid alterations at membrane surfaces during stress. Moreover, by binding to PI(4,5)P2 Rab18 could take part in the regulation of different cellular processes, showing a new role of dehydrins as regulators of plant stress. A possible role of Rab18 in the regulation of ABA induced stomata movements are presented.