Abstract
Microglia are the primary innate immune cells of the central nervous system and act as dynamic regulators of neural development, homeostasis, and response to injury. This review summarizes key discussions from the Glial Club South Cone Meeting 2025, focusing on (i) mechanisms and regulation of microglial phagocytosis and its dual role in tissue repair and neurodegeneration, (ii) the emerging immunometabolic and neuroprotective functions of the lipid-sensing receptor CD300f in aging and Alzheimer’s disease models, and (iii) the context-dependent roles of autophagy in microglial activation, inflammation control and proteostasis. We highlight how phagocytic signaling (IFN, IL-6, “eat-me,” “don’t-eat-me” cues), immune receptors and epigenetic regulation shape microglial states and function. Translational implications are discussed, including strategies to preserve beneficial microglial functions while limiting detrimental phagoptotic and pro-inflammatory responses. Identifying receptor-specific ligands, clarifying causal roles of phagocytosis in neurodegeneration, and dissecting autophagy-dependent quality-control pathways emerge as priority areas for future research.