APOE and early-onset autosomal dominant Alzheimer disease: Looking further into the biological functions of the novel ATE1 substrates, CLU has caught our attention because it is the most cited gene among the four and has been identified as the third greatest late onset Alzheimer’s disease (LOAD) risk gene following APOE and BIN1. CLUS, a normally secreted protein, has been found intracellularly under certain stress conditions, and its biological roles have been implicated in lipid transport and immune modulation as well as its prominent extracellular chaperone function [36].