To fill the gaps in the verification of in vivo and in vitro correlations, the aim of this study was to examine the impact of human TAS1R2/TAS1R3 polymorphisms (located in the coding sequences) identified in a literature review and associated with obesity and/or high sugar intake on the functionality of the sweet taste receptor stimulated by 12 different sweeteners selected for the SWEET project. Here, TAS1R3 is linked to obesity due to melanocortin 4 receptor deficiency.