Lipid droplets are complex and dynamic intracellular organelles that have an essential role in cholesterol and lipid homeostasis, and profoundly affect cellular structure and function. Variations in lipid-droplet composition exist between different cell types, but whether there are differences in the mechanisms of lipid-droplet accumulation remains to be elucidated. Here, we report that P311, previously identified to have a function in neuronal regeneration and a potential role in distal lung generation, regulates lipid droplet accumulation. P311 upregulates several classes of genes associated with lipid synthesis, significantly increases intracellular cholesterol and triglyceride levels, and increases intracellular lipid droplets. Interestingly, P311 expression is not necessary for lipogenesis in the well-established NIH3T3-L1 cell model of adipogenic differentiation. Instead, we demonstrate a novel role for P311 in an alternative pathway of lipid-droplet accumulation that is induced by the regeneration-inducing molecule retinoic acid.