TREM2 is a premier example of how mutations in a microglial receptor can lead to aberrant innate immune cell signaling that contributes to the initiation and propagation of neurodegenerative phenotypes including NHD/PLOSL [10, 11], FTD [12–17], AD [13, 17–23], PD [14], ALS [24], and essential tremor [25]. The gene discussed is TREM2; the disease is Nasu-Hakola disease.