Lipid droplets: Open questions and conceptual advances around a unique organelle

Once viewed as mere lipid inclusions, the past four decades have witnessed an explosion of research into lipid droplet (LD) biogenesis and function. Pioneering cell biology, biochemical, genetics, and lipidomic studies now reveal LDs as active players in lipid metabolism and cellular homeostasis. Here, we discuss some of the major findings that defined LDs as bona fide organelles. However, despite what is known, much needs to be discovered. We highlight five enduring questions that continue to challenge the LD field and discuss a few misconceptions about this remarkable organelle.