Microglial phagoptosis in development, health, and disease

Microglial phagoptosis, defined as the phagocytosis of a viable cell by microglia that ultimately causes the death of the engulfed cell, has emerged as a pivotal process in sculpting neural circuits within the central nervous system (CNS). Essential for neurodevelopmental circuit refinement and ongoing tissue homeostasis, this process relies on dynamic molecular cues that direct microglia to specific cellular substrates. Physiologically, phagoptosis contributes to neural circuit refinement and cell number regulation during development; however, its dysregulation can drive neurodevelopmental and neurodegenerative disorders via aberrant cell removal. Recent advances have elucidated the distinct signaling pathways involved in target recognition and engulfment, revealing the dual roles of microglial phagoptosis in both CNS health and disease. Deeper mechanistic insight into this process offers new therapeutic opportunities for conditions characterized by defective or excessive cell clearance. This review summarizes current progress, highlights unresolved challenges, and discusses future perspectives on targeting microglial phagoptosis for intervention in CNS disorders.