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Sweet Taste Receptors (STRs) are G-protein coupled receptors (GPCRs) formed by the obligate heterodimerization of TAS1R2 and TAS1R3. STRs have historically been associated with sensing sugars in the tongue, as well as metabolic regulation in the gut and pancreas. However, recent research has shown that STRs are present across the body in organs such as the brain, heart, and skeletal muscle. Herein, I will focus on the presence of STRs in skeletal muscle to further investigate previous findings that TAS1R2 deletion increases muscle mass and fitness in mice. Using Crispr-Cas9 gene editing, the TAS1R2 gene was deleted from a C2C12 muscle cell line (cKO). Following a standard differentiation protocol, cKO cultures showed minimal signs of differentiation. However, when differentiated in the presence of insulin, cKO cultures formed a novel phenotype containing myofibers 3x the thickness of cWT counterparts. Under q-PCR analysis, there was a consistent upregulation of key myogenic progenitors Pax7 and MyoD in cKO cells, alongside significant downregulation of myogenic transcription factors Klf2 and Klf4 which are necessary for mediating fusion. These findings suggest a potential regulation of the ERK5-Klf2/4 signaling axis by TAS1R2. These results corroborate the previous findings in the mouse model, indicating that deletion of STR signaling enhances myofiber size and muscle mass under physiological conditions. This is of strong clinical relevance to the loss of muscle mass that is symptomatic of both obesity and aging. Furthermore, STRs are a promising treatment pathway since GPCRs are well proven therapeutic targets.