Several lines of evidence connect S2R to Alzheimer’s disease; these include its localization to neuronal synapses, amyloid-β oligomers, and learning and memory (Figure 2, Table 1), including data from studies genetically or pharmacologically manipulating S2R constituents and interacting proteins, including PGRMC1. Here, PGRMC1 is linked to early-onset autosomal dominant Alzheimer disease.