Lipid droplets (LD) are diverse and essential organelles that function as cellular cores of lipid and energy homeostasis. A precise measurement of the composition of LD proteins and lipids and their functional characterization is critical for understanding the physiology of LD and their role in human disease. This Methods Collection aims to develop novel approaches to precisely identify LD proteins in homogenous and heterogeneous populations of LDs and quantify the components of the LD proteins under different metabolic conditions. In addition, this collection will accept manuscripts describing the methods of isolating LDs, the mechanisms and pathways that regulate the formation and composition of LD proteins in different cell types, and how they contribute to the development of metabolic diseases such as obesity, diabetes, and fatty liver disease.