Microglia are resident phagocytes of the central nervous system that play an essential role in brain development and homeostasis. When the intracellular lipid content exceeds the metabolic capacity of microglia, lipid droplets accumulate, giving rise to a distinct population termed lipid-laden microglia (LLMs). LLMs have been implicated in various neuroinflammatory and neurodegenerative diseases, functioning as both regulators/indicators of inflammation and potential therapeutic targets. This review summarizes the current research on LLMs, focusing on disease-specific regulators and functions, protective roles, interactions with neighboring cells, and advances in diagnostic and analytical tools. We also discuss the blurred distinction between LLMs and macrophages, inconsistent terminology, and major knowledge gaps across different disease contexts. Deciphering the composition, formation, and dynamics of lipid droplets in microglia is critical for uncovering how microglial states shift under diverse pathological stimuli. A clearer view of these mechanisms may reveal novel roles of LLMs and open new avenues for therapeutic intervention.
Keywords: lipid droplet analytical tools; lipid droplets; lipid metabolism; microglia; neurodegeneration.