An inside job: New roles for ApoE at the lipid droplet

Abstract

The secreted ApoE protein is a major regulator of lipid transport between brain cells. In this issue, Windham et al. (https://doi.org/10.1083/jcb.202305003) uncover a novel intracellular role for ApoE at the lipid droplet surface, where it regulates lipid droplet size and composition.

Figure 1.

ApoE regulates LD dynamics. ApoE undergoes co-translational translocation into the ER lumen, where it enters the secretory route. Once secreted, ApoE regulates lipid transport between different brain cells. Windham and colleagues now show that upon a fatty acid challenge, ApoE escapes translocation into the ER and is recruited to newly formed LDs. In absence of ApoE, or in the presence of the AD risk variant ApoE4, LDs become larger and have increased levels of unsaturated triglycerides that are more sensitive to lipid peroxidation.