In light of our experimental observations, we believe this is best explained by the hypothesis that another interaction (such as TREM2 binding to GAGs, which we show here is impacted by these AD risk variants) is required to mediate phospholipid signaling; thus in the context of cellular experiments, TREM2 R47H shows diminished signaling, while in direct lipid-binding assays it performs in the same way as WT TREM2. The gene discussed is TREM2; the disease is Alzheimer disease.