Functional assays that use the T1R3 receptor to screen for taste modulatory compounds are provided. These assays include cell-based assays and high throughput functional assays that identify compounds which activate or modulate T1R3 receptor activation. Preferred functional assays detect the effect of a putative taste modulatory compound on intracellular voltage or intracellular calcium of a cell that expresses TIR3 polypeptide, preferably in association with a G protein, e.g. Gdl5. The compounds identified in such functional assays potentially have application as taste modulators and potential flavor enhancers or modulators for additives to foods and beverages for human or animal consumption.