Because of prevalence of branched cells with high membrane/volume ratio and the presence of lipid-rich myelin, brain has higher level of lipids than any other tissue except the adipose. Importance of lipid for brain structure and function is further reflected in its unique lipid composition and the exceptional diversity of lipid species present in the neural tissue. Lipids are major structural components of cellular and organellar membranes, affecting their structure, fluidity and barrier function. Many lipids also play important roles in cellular signaling, either by themselves functioning as signaling intermediates, or via impact on the formation and function of lipid rafts which serve as docking platforms for intracellular signaling molecules. Lipids dynamically reside in multiple intracellular locations and their organellar distribution is important for specific interactions and biological function. Different organellar compartments also create specialized local environments that facilitate interactions between lipids and other macromolecules such as proteins to facilitate physiological processes. Therefore, intracellular localization has to be taken into account when determining the importance of changes in lipid abundance and function. In order to determine the role of lysosomal lipids during brain aging, we compared lipid profiles of lysosomes purified from young (3-month), middle aged (12-month) and aged (18- and 24-month) mouse brains. We observed significant accumulation of several groups of sphingolipids, including ceramides, hexCer and sphingomyelins. These changes resemble those previously reported in lysosomal storage diseases and correlate with functional and cognitive changes. Lipid changes were accompanied by profound proteome alterations which included accumulation of several proteins implicated in lysosomal storage diseases and neurodegenerative diseases. We further compare lysosomal changes occurring during normal brain aging and brain aging perturbed following early life exposure to traumatic brain injury, a known factor predisposing to development of neurodegenerative disease or aging in mouse models of AD and lysosomal storage disease GRN.