Lipid droplets (LD) are functionally conserved fat storage organelles found in all cell types. LDs have a unique structure comprising of a hydrophobic core of neutral lipids (fat), triacylglycerol (TAG) and cholesterol esters (CE) surrounded by a phospholipid monolayer. LD surface is decorated by a multitude of proteins and enzymes rendering this compartment functional. Accumulating evidence suggests that LDs originate from discrete ER-subdomains, demarcated by the lipodystrophy protein seipin, however, the mechanisms of which are not well understood. LD biogenesis factors together with biophysical properties of the ER membrane orchestrate spatiotemporal regulation of LD nucleation and growth at specific ER subdomains in response to metabolic cues. Defects in LD formation manifests in several human pathologies, including obesity, lipodystrophy, ectopic fat accumulation, and insulin resistance. Here, we review recent advances in understanding the molecular events during initial stages of eukaryotic LD assembly and discuss the critical role of factors that ensure fidelity of this process.

脂滴（LD）是所有细胞类型中都存在的功能保守的脂肪储存细胞器。LD 具有独特的结构，由中性脂质（脂肪）、三酰甘油 (TAG) 和胆固醇酯 (CE) 的疏水核心组成，周围环绕着磷脂单层。LD 表面由多种蛋白质和酶修饰，使该隔室发挥功能。越来越多的证据表明，LD 源自离散的 ER 子结构域，由脂肪营养不良蛋白 seipin 划分，然而，其机制尚不清楚。LD 生物发生因子与 ER 膜的生物物理特性一起协调 LD 成核和特定 ER 子域生长的时空调节，以响应代谢线索。LD 形成的缺陷表现在多种人类病理学中，包括肥胖、脂肪营养不良、异位脂肪堆积和胰岛素抵抗。在这里，我们回顾了理解真核 LD 组装初始阶段分子事件的最新进展，并讨论了确保该过程保真度的因素的关键作用。