Oligodendroglia support axon survival and function through mechanisms independent of myelination, and their dysfunction leads to axon degeneration in several diseases. The study shows that the most abundant lactate transporter in the central nervous system (CNS), monocarboxylate transporter 1 (MCT1), is highly enriched in oligodendroglia. Disruption of MCT1 causes axon damage and neuron loss in animal and cell culture models. MCT1 is also reduced in patients and mouse models of amyotrophic lateral sclerosis (ALS), suggesting a role for oligodendroglial MCT1 in pathogenesis. This study defines a new fundamental mechanism by which oligodendroglia support neurons and axons. Oligodendroglia support axon function and neuron survival through lactate transport, which is essential for axonal energy supply. MCT1 is primarily localized to oligodendroglia in the CNS, and its expression is significantly higher in oligodendroglia compared to astrocytes. MCT1 deficiency in vivo leads to motoneuron death, and MCT1 heterozygote null mice develop CNS axonopathy without demyelination or oligodendrocyte injury. These findings suggest that MCT1 is critical for the normal function of CNS axons through a myelin-independent mechanism. In ALS, reduced MCT1 expression in oligodendroglia may contribute to neurodegeneration. The study shows that MCT1 expression is reduced in affected regions of ALS patients and in SOD1 transgenic mice, which are commonly used models of ALS. These results suggest that alterations in oligodendrocyte MCT1 may contribute to motoneuron degeneration in ALS. The study highlights the critical role of MCT1 in maintaining axon function and neuron survival. MCT1 is essential for lactate transport from oligodendroglia to axons, and its disruption leads to axon degeneration. The findings provide new insights into the role of oligodendroglia in axon function and neurodegeneration, and suggest that MCT1 is a potential therapeutic target for diseases such as ALS.Oligodendroglia support axon survival and function through mechanisms independent of myelination, and their dysfunction leads to axon degeneration in several diseases. The study shows that the most abundant lactate transporter in the central nervous system (CNS), monocarboxylate transporter 1 (MCT1), is highly enriched in oligodendroglia. Disruption of MCT1 causes axon damage and neuron loss in animal and cell culture models. MCT1 is also reduced in patients and mouse models of amyotrophic lateral sclerosis (ALS), suggesting a role for oligodendroglial MCT1 in pathogenesis. This study defines a new fundamental mechanism by which oligodendroglia support neurons and axons. Oligodendroglia support axon function and neuron survival through lactate transport, which is essential for axonal energy supply. MCT1 is primarily localized to oligodendroglia in the CNS, and its expression is significantly higher in oligodendroglia compared to astrocytes. MCT1 deficiency in vivo leads to motoneuron death, and MCT1 heterozygote null mice develop CNS axonopathy without demyelination or oligodendrocyte injury. These findings suggest that MCT1 is critical for the normal function of CNS axons through a myelin-independent mechanism. In ALS, reduced MCT1 expression in oligodendroglia may contribute to neurodegeneration. The study shows that MCT1 expression is reduced in affected regions of ALS patients and in SOD1 transgenic mice, which are commonly used models of ALS. These results suggest that alterations in oligodendrocyte MCT1 may contribute to motoneuron degeneration in ALS. The study highlights the critical role of MCT1 in maintaining axon function and neuron survival. MCT1 is essential for lactate transport from oligodendroglia to axons, and its disruption leads to axon degeneration. The findings provide new insights into the role of oligodendroglia in axon function and neurodegeneration, and suggest that MCT1 is a potential therapeutic target for diseases such as ALS.