**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** HEMIPTERAN VECTORS ARE ECONOMICALLY IMPORTANT PLANT-SUCKING PESTS WITHIN AGRICULTURAL SYSTEMS AND THEIR POPULATIONS ARE EXPECTED TO INCREASE DUE TO SHIFTING GLOBAL WEATHER PATTERNS THAT ACCELERATE INSECT POPULATION GROWTH. TO BOLSTER THE TOOLBOX FOR CONTROLLING HEMIPTERAN VECTORS, WE HAVE FOCUSED ON IDENTIFYING NOVEL PHYSIOLOGICAL PATHWAYS THAT SIMULTANEOUSLY INHIBIT FEEDING, HALT PATHOGEN TRANSMISSION, AND INDUCE MORTALITY. WE PREVIOUSLY DEMONSTRATED THAT CHEMICAL INHIBITORS OF INWARD RECTIFIER POTASSIUM (KIR) REDUCE FUNCTION OF APHID SALIVARY GLANDS, ELIMINATE PHLOEM FEEDING EVENTS, AND LEAD TO DEATH THROUGH STARVATION. HOWEVER, SIGNIFICANT GAPS IN KNOWLEDGE REMAIN REGARDING THE TOXICOLOGICAL RELEVANCE OF HEMIPTERAN KIR CHANNELS AND FURTHER, THE SALIVARY GLAND REMAINS AN UNEXPLOITED TARGET SITE FOR HEMIPTERAN CONTROL. THUS, THE GOAL OF THIS PROPOSAL IS TO TEST THE HYPOTHESIS THAT INDUCING SALIVARY GLAND FAILURE THROUGH KIR CHANNEL INHIBITION REPRESENTS A VIABLE APPROACH TO REDUCING HEMIPTERAN-MEDIATED FEEDING DAMAGE IN AGRICULTURAL SYSTEMS. TO ACHIEVE THIS GOAL, WE PROPOSE THE FOLLOWING OBJECTIVES: 1) TEST THE EFFICACY OF STRUCTURALLY DIVERSE KIR CHANNEL INHIBITORS TO INHIBIT AND/OR ALTER SALIVARY SECRETIONS TO PREVENT PLANT FEEDING BY HEMIPTERAN VECTORS; 2) DETERMINE THE ABILITY OF KIR CHANNEL INHIBITORS TO PREVENT PATHOGEN TRANSMISSION AND ACQUISITION BY HEMIPTERAN VECTORS; 3) ENHANCE PLANT SYSTEMICITY OF KIR CHANNEL INHIBITORS THROUGH NOVEL BOTANICAL SOLUBILIZERS. COLLECTIVELY, THESE DATA WILL FURTHER VALIDATE HEMIPTERAN KIR CHANNELS AND THE SALIVARY GLAND AS TRACTABLE TARGETS FOR AGROCHEMICAL DEVELOPMENT. WE AIM TO INCREASE THE SUSTAINABILITY OF THE AGRICULTURAL INDUSTRY THROUGH MANAGEMENT OF HEMIPTERAN POPULATIONS AND THUS, THIS PROJECT SUPPORTS THE PRIORITIES LISTED IN THE PROGRAM CODE A1112.