Major routes of endocytosis involved in lipoprotein uptake. Clathrin-dependent endocytosis employs clathrin recruited by adaptor protein, AP2, along with receptors to bind and concentrate cargo in coated pits. Clathrin polymerisation promotes membrane invagination, and along with the BAR proteins, stabilise vesicle formation. Dynamin recruited by the BAR proteins facilitates release of the vesicle. Caveolin-dependent endocytosis utilises the cholesterol-binding caveolin protein to form caveolae (little caves) in which receptors are concentrated. Binding of the cargo to its receptor initiates budding and release of the caveolae via various kinases and phosphatases leading to internalisation. Macropinocytosis constitutes a non-specific form of cargo capture which is driven by calcium sensing or activation of receptor tyrosine kinases (RTKs) to drive actin polymerisation via Rac and Rho GTPases. This promotes membrane ruffling and formation of a macropinosome which imbibes localised cargo and associated fluid. Internalised cargo, regardless of the endocytic route of entry, is then trafficked and sorted via the endosomal system to various destinations. Transcytosis (not shown) is usually initiated by one of these three endocytic routes followed by trafficking of the encapsulated cargo across the cell and exit via exocytosis.