LSD are genetic or acquired diseases characterized by anomalous accumulation of metabolites in the lysosomes. Increased levels of intralysosomal metabolites leads to cell malfunction and cell death. We have identified vesicular trafficking and autophagy mechanisms that, when impaired, are associated with the development of abnormal levels of endoplasmic reticulum stress (ER stress) in LSDs. We have special interest in developing strategies directed at upregulating the vesicular trafficking pathways of cells that have accumulated metabolites in their lysosomes to restore normal cellular function and prevent cell death. We are currently exploring several trafficking pathways and utilizing high-throughput screening approaches to identify potential novel therapies for the treatment of LSDs