Our original finding that ApoE isoforms can differentially impair synapse functions by trapping postsynaptic (and possibly also presynaptic) recycling vesicles that contain ApoE receptors was inspired by the original observations of Heeren, Beisiegel and colleagues who first described a prolonged intracellular retention of ApoE4 in a hepatoma cell line (Heeren et al., 2004). The gene discussed is APOE; the disease is hepatocellular carcinoma.