Monosialodihexosylganglioside synthase deficiency (GM3SD) is a neurological disease that is caused by a loss-of-function mutation(s) in the ST3 betagalactoside alpha-2,3-sialyltransferase 5 (ST3GAL5) gene. Knockout (KO) models have been made to track biochemical and physiological phenotypes of GM3SD. However, recapitulation of disease pathophysiology, including mechanistic links in both models, requires additional research for full understanding. A gene therapy approach for GM3SD using recombinant adenoassociated viral vectors (rAAVs) is being worked on, and assessment of its efficacy is required before progressing to clinical trials. The goals of the current research are to 1) assess the ability of rAAV-treatment on rescuing a wellcharacterized hearing phenotype in the St3gal5-/- single-knockout (SKO) mouse model; 2) delve into potential cross-correction mechanisms observed in this specific neurological disease; and 3) use current advancements in glycolipid research for characterizing ganglioside profiles and assessing metabolic rescue in the disease models, with and without rAAV treatment. Taken together this research will help to further our understanding of GM3SD as a neurological and metabolic disorder, as well as how rAAV can rescue phenotypes associated with the disease.