Olfactory receptors (ORs) are G protein-coupled receptors which serve to detect odorants in the nose. It is now appreciated that these receptors have roles beyond the canonical smell response and serve important functions in a number of different tissues. The epithelial lining of the kidney must carefully monitor the composition of the tubular fluid as it moves through the different segments of the nephron; thus, it is well suited to take advantage of sensory receptors such as ORs in order to maintain homeostasis. Among the growing list of ORs known to be expressed in the kidney is olfactory receptor 1393 (Olfr1393). We recently determined that Olfr1393 is found on the apical membrane of the proximal tubule where it contributes to renal glucose handling as a novel regulator of sodium glucose co-transporter 1 (Sglt1) localization. Glucose reabsorption in the proximal tubule (via Sglt1 and Sglt2) has emerged as an important contributor to the development of diabetes. Inhibition of Sglt2 is now accepted as a viable therapeutic treatment option for patients with type II diabetes and has been shown to delay diabetic kidney disease. We hypothesized that Olfr1393 may contribute to the progression of type II diabetes, particularly the development of hyperfiltration which has been linked to increased Na+ reabsorption in the proximal tubule via the Sglts. To test this, Olfr1393 wildtype (WT) and knockout (KO) C57BL6 mice were challenged with a high fat diet (HFD) to induce early stage type II diabetes. After 16 weeks on the HFD, WT mice displayed increased fasting blood glucose values and impaired glucose tolerance. Both of these effects were significantly blunted in the male KOs. In addition, both male and female WT mice presented with an increased glomerular filtration rate (via transcutaneous measurement of FITC-Sinistrin clearance) over time indicating that they developed diabetes-induced hyperfiltration, and this response was attenuated in the Olfr1393 KO mice. Collectively, this data indicates that renal Olfr1393 can contribute to the progression of type II diabetes. Outside of the kidney, Olfr1393 is expressed in several other tissues including the liver, the major site of glucose metabolism. Given this, it is possible that Olfr1393 and other ORs function as regulators of glucose homeostasis in other tissues as well. Using a TaqMan real time PCR assay, we identified a total of 17 murine ORs with detectable expression in the liver including Olfr1393. Efforts are currently underway to determine how these receptors contribute to liver physiology and glucose homeostasis in both health and disease.