While it is speculated that phosphorylation may change the interaction of PICALM with its binding partners such as R-SNAREs, PtdIns(4,5)P2 or clathrin, it remains elusive which kinases are involved in PICALM phosphorylation, whether PICALM phosphorylation is misregulated during the progression of AD, whether PICALM phosphorylation has any impact on its protein stability/degradation or its subcellular localization and whether phosphorylation of PICALM may cause a loss of function and/or a gain of toxicity. This evidence concerns the gene PICALM and Alzheimer disease.