Core Viewpoint - The research highlights the critical role of TMEM119 in maintaining microglial homeostasis and regulating the progression of Alzheimer's disease (AD), suggesting innovative therapeutic strategies targeting this pathway [2][3][4]. Group 1: Research Findings - The study published in the journal Immunity elucidates the mechanism by which TMEM119 interacts with amyloid-β (Aβ) to promote its clearance in a mouse model of AD [2][3]. - TMEM119 expression decreases with Aβ deposition, correlating positively with the progression of AD in mice, and its absence accelerates the transition of microglia to a disease-associated state [4][5]. - Overexpression of TMEM119 enhances microglial phagocytic activity, and two small molecules, Kartogenin and SRI-011381, can improve cognitive function in mid-stage AD mice by enhancing TMEM119 expression [4][5]. Group 2: Comparison with Other Receptors - The study compares TMEM119 with another important Aβ receptor, TREM2, noting that TREM2 deficiency blocks the transition of microglia from homeostasis to a disease-associated state, while TMEM119 deficiency leads to a loss of homeostasis and accelerates the transition to an earlier disease-associated state [4][5]. Group 3: Implications for Treatment - The research indicates that restoring microglial homeostasis through TMEM119 presents a promising therapeutic avenue for AD, with significant clinical translation potential despite the need for further optimization of the candidate compounds [5].