Annexin A2 is a peripheral membrane protein that belongs to the annexin family of Ca2+ and phospholipid-binding proteins. This protein, which plays a role in membrane organization and dynamics in particular along the endocytic pathway, exists as a heterotetrameric complex, consisting of two annexin A2 molecules bound via their N-termini to a dimer of p11/S100A10 light chains. The light chain, and thus presumably formation of the heterotetramer, was reported to control annexin A2 association to the plasma membrane and to cortical actin, as well as the distribution of recycling endosomes. However, the specific role of the light chain and the functions of monomeric versus heterotetrameric annexin A2 have remained elusive in the endocytic pathway.