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Lipid droplets (LDs) are dynamic cellular hubs of lipid metabolism. While LDs contact a plethora of organelles, they have the most intimate relationship with the endoplasmic reticulum (ER). Indeed, LDs are initially assembled at specialized ER subdomains, and recent work has unraveled an increasing array of proteins regulating ER-LD contacts. Among these, seipin, a highly conserved lipodystrophy protein critical for LD growth and adipogenesis, deserves special attention. Here, we review recent insights into the role of seipin in LD biogenesis and as a regulator of ER-LD contacts. These studies have also highlighted the evolving concept of ER and LDs as a functional continuum for lipid partitioning and pinpointed a role for seipin at the ER-LD nexus in controlling lipid flux between these compartments.

Seipin-Mediated Contacts as Gatekeepers of Lipid Flux at the Endoplasmic Reticulum–Lipid Droplet Nexus