As aberrant calcium homeostasis and lipid metabolism have been observed in Alzheimer's disease [45,46] and FE65 is implicated in the pathogenesis of the disease [3], it is worthwhile to determine the roles of the ARF6-ARNO-FE65-ELMO1-DOCK180 multimeric complex in both physiological and pathological conditions. Here, CYTH2 is linked to early-onset autosomal dominant Alzheimer disease.