Dysregulated lipid homeostasis is a characteristic of brain aging and age-related neurodegenerative diseases. Perilipins, a family of proteins decorating the surface of lipid droplets (LDs), are key regulators of lipid metabolism in peripheral organs. Research indicates that the expression of perilipin2 increases in the brain with neurodegenerative diseases, such as Alzheimer’s disease, and preliminary data from our group suggest a reduced LD size in hippocampal neurons in response to the deletion of perilipin2. This project aims to investigate the connection between aging and the accumulation of lipids in LDs in the hippocampus, and whether perilipin2 is an important regulator of this LD accumulation. Brain sections from aged perilipin2 knockout mice and their wild-type littermates (> 1 year old) were analyzed with confocal microscopy to demonstrate the effects of perilipin2 on the LD accumulation in the aged brain. Further, RNA sequencing on hippocampal tissue from the same mice shed light on the common mechanisms underlying LD pathology and whether perilipin2 is involved in the regulation of LDs in brain cells and alterations in markers of brain aging.