Lipid droplets, an enigmatic organelle under the spotlight

Lipid droplets (LDs) are intracellular organelles that dynamically regulate lipid and energy homeostasis, mediate hormone production, produce inflammation signaling, while also participating in numerous biological processes and activities. Dysregulation of LD homeostasis is linked to various diseases, such as lipodystrophy, obesity, type 2 diabetes (T2D), cardiovascular diseases (CVD), metabolic dysfunction-associated steatotic liver disease (MASLD), neuronal diseases, and among others. The core of LDs consists of neutral lipids, including triacylglycerol (TAG), cholesteryl esters (CE), and retinyl esters (RE), which are encircled by a monolayer of phospholipid membrane decorated with a subset of LD proteins, both resident as well as dynamic, that vary in different cells, tissues, organs, and organisms. Over the past two decades, together with technological advances, significant achievements have been made in understanding LD biology, including their lifecycle: such as biogenesis, growth/expansion, fusion, and degradation, as well as their diversity and heterogeneity, under both physiological and pathological conditions. In this review, we summarize the current knowledge and methodologies of LD biology in animal cells, and also provide guiding questions, hopefully bringing new directions for future study of LDs and for potential therapeutic treatments for LD-related human diseases.