A long-term goal of my laboratory is to address mechanisms of cellular fatty acid metabolism and their implication in neuronal functions. Fatty acids are essential for life but are toxic in their free form, as they can readily transform into highly bioactive, cytotoxic lipid species that can lead to cell death and organ dysfunction. To deal with this challenge, most organisms convert an excess amount of free fatty acid into neutral lipid forms and store them in cellular organelles called lipid droplets (LDs). Much effort has focused on defining and elucidating the pathways governing LD formation, but less is known about how fatty acids are released from LDs in (patho)physiological circumstances. We aim to address these fundamental unsolved problems in cell biology: the molecular mechanisms and roles of lipid recycling pathways and how different cell types in the brain utilize these pathways to regulate neuronal functions. The main three questions we focus on are 1) What are the regulatory mechanisms underlying the autophagic lipid degradation pathway (lipophagy)? 2) How do lipids traffic within the cells and get utilized at inter-organelle membrane contact sites? and 3) What are the roles of lipophagy in neuronal lipid metabolism and neuropathology? To tackle the unique properties of LDs composed of neutral lipids surrounded by a monolayer of phospholipids, we employ multidisciplinary approaches encompassing advanced microscopy, biochemistry, biophysics, and mass spectrometry-based analytics. Successful completion of our study will reveal fundamental principles of lipid recycling mechanisms and contribute to the development of potential therapeutic strategies focusing on defective lipid metabolism in various neurodegenerative disorders.