Cytoplasmic lipid droplets are nearly ubiquitous intracellular structures that store fat for combustion on site or in distant tissues. Droplets, which bud from the ER and consist of a core of neutral lipids, typically triacylglycerol (TG) and steryl esters (SEs), are surrounded by a phospholipid monolayer and associated proteins.

The formation of droplets is not spontaneous but is facilitated by ER proteins and specific lipids. Seipin, a protein that resides at ER–droplet junctions, functions early to stabilize the nascent structures, ensures droplets of correct morphology, prevents the accumulation of phosphatidic acid at the ER–droplet junction, and prevents ectopic budding into the nucleus (Cartwright et al., 2015; Grippa et al., 2015; Wolinski et al., 2015; Wang et al., 2016). Fit2, fat storage–inducing transmembrane protein 2, binds to TG and ensures that the expansion of the neutral lipid core in nascent droplets is toward the cytosolic rather than the luminal surface (Gross et al., 2011; Choudhary et al., 2015). Proteins that bind to budding droplets from the cytosolic surface may also facilitate droplet formation: Plin3 and Plin4 bind early to droplets, suggesting that they may function early in droplet formation (Wolins et al., 2003; Skinner et al., 2009). Indeed, droplets fail to mature in the absence of Plin3 (Bulankina et al., 2009). In addition to these proteins, DAG has also been shown to be important for droplet budding (Skinner e t al., 2009; Adeyo et al., 2011).