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Synchronous and timely regulation of multiple genes results in an effective defense response that decides the fate of the host when challenged with pathogens or unexpected changes in environmental conditions. One such gene, which is downregulated in response to multiple bacterial pathogens, is a putative nonspecific lipid transfer protein (nsLTP) of unknown function that we have named DISEASE RELATED NONSPECIFIC LIPID TRANSFER PROTEIN 1 (DRN1). We show that upon pathogen challenge, DRN1 is strongly downregulated, while a putative DRN1-targeting novel microRNA (miRNA) named DRN1 Regulating miRNA (DmiR) is reciprocally upregulated. Furthermore, we provide evidence that DRN1 is required for defense against bacterial and fungal pathogens as well as for normal seedling growth under salinity stress. Although nsLTP family members from different plant species are known to be a significant source of food allergens and are often associated with antimicrobial properties, our knowledge on the biological functions and regulation of this gene family is limited. Our current work not only sheds light on the mechanism of regulation but also helps in the functional characterization of DRN1, a putative nsLTP family member of hitherto unknown function.