Within a few years following the onset of fractures, these patients begin to exhibit cognitive decline and other neurodegenerative changes.131,132,135 Research indicates that mutations in the TREM2 gene are a significant cause of Nasu-Hakola disease.136 The TREM2-DAP12 signaling pathway in microglial cells is involved in cell survival, phagocytosis, and the actin reorganization required for cell activation and phagocytic activity. The gene discussed is TYROBP; the disease is Nasu-Hakola disease.