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Gangliosides are sialylated glycosphingolipids highly enriched in the central nervous system, where they regulate membrane signaling, metabolism, neurogenesis, and immune responses. This Review integrates recent advances across distinct experimental and clinical domains. First, recent studies demonstrate that the monosialoganglioside GM1 enhances astrocyte-neuron metabolic coupling via the astrocyte-neuron lactate shuttle, thereby supporting neuronal bioenergetics and resilience. Complementary mechanistic work shows that specific gangliosides regulate adult neurogenesis through developmentally controlled epigenetic and transcriptional programs. In Huntington's disease models, preclinical evidence indicates that GM1 and related gangliosides attenuate microglia-mediated inflammatory responses and promote proteostasis through extracellular vesicle-dependent clearance of misfolded proteins. Finally, clinical evidence from acute spinal cord injury demonstrates that GM1 administration accelerates neurological recovery, underscoring its translational relevance. Together, these findings position gangliosides as multi-target modulators of neural repair and inflammation, and highlight their potential for therapeutic development.