Tusc5 is a transmembrane protein that assists trafficking of Glucose transporters molecules in adipocites. We and others have previously described Tusc5 in projection sensory neurons. Glut4 transporters (localized in muscles and adipocytes) are continuously recycled through endosomes from and to the plasma membrane and stored in GSVs (Glut4 Storage Vesicles). In adipocites, Tusc5 follows Glut4 trafficking between GSVs and cell surface, upon insulin stimulation. Tusc5 interacts with the signaling cascade of fusion of GSVs with the plasma membrane, similar to the exocytosis mechanism in neuronal synapses.We have recently generated a conditional knock-in Tusc5eGFP allele in mice, in order to study the role of Tusc5 in supporting neuronal metabolism, and its involevement in the mechanisms of diabetic retinopathy and neuropathy. Using these mice we found that Tusc5 ablation in specific sensory neuron populations results in electrophysiological defects that progress with age. Mice lacking Tusc5 from all cells of the body have normal fasting Glucose levels, but exhibit altered Glucose clearance in Glucose Tolerance Tests. Insulin Tolerance curves are insignificantly affected up to 7 months of age. When challenged with standard High Fat Diet, Tusc5 mice surprisingly loose weight, display neurological symptoms and altered GTT and ITT profiles compared to wild type animals. These results suggest an involvement of Tusc5 in energy metabolism and its pathological effects on neurons. Funding : Unitatea Executiva pentru Finantarea Invatamantului Superior, a Cercetarii, Dezvoltarii si Inovarii Grant PN-III-P4-PCE-2021-0333 (DP, AMT, VV & TCB)