Ó³»­´«Ã½

How proteins specifically localize to the phospholipid monolayer surface of lipid droplets (LDs) is being unraveled. We review here the major known pathways of protein targeting to LDs and suggest a classification framework based on the localization origin for the protein. Class I proteins often have a membrane-embedded, hydrophobic 'hairpin' motif, and access LDs from the endoplasmic reticulum (ER) either during LD formation or after formation via ER-LD membrane bridges. Class II proteins access the LD surface from the cytosol and bind through amphipathic helices or other hydrophobic domains. Other proteins require lipid modifications or protein-protein interactions to bind to LDs. We summarize knowledge for targeting and removal of the different classes, and highlight areas needing investigation.