 ApoE binding leads to the cleavage of ApoER2 into secreted proteins by the actions of the plasma membrane protein gamma secretase.ApoE may be the signalling ligand responsible for ApoER2's role in modulating the JNK signalling pathway.FE65 is an intracellular protein that binds to the NPXY motif of ApoER2 and plays a role in linking other proteins, such as amyloid precursor protein, to ApoER2.