GLD, also known as Krabbe Disease, is a lysosomal storage disease caused by loss-of-function mutations in the lysosomal hydrolase, GALC, which breaks down galactosylceramide (galcer), a major constituent of myelin in the nervous system (Figure 1). GALC dysfunction results in the lysosomal accumulation of lipids like galcer and its toxic metabolite, psychosine. These lipids are thought to result in extensive demyelination and cell death. Brain macrophages also accumulate these lipids and worsen disease pathology. More recently, these cells were found to adopt proinflammatory states (Figure 2, 3). GALC-deficient macrophages worsen disease and adopt proinflammatory states, while GALC-competent cells ameliorate pathology. However, how GALC deficiency leads to abnormal macrophage responses is unknown. The current treatment, hematopoietic stem cell transplant (HSCT) successfully delays disease progression but has limitations such as a narrow treatment window and high mortality. Discovering the mechanisms underlying macrophage dysfunction will be key to the development of safer therapies for GLD. Additionally, our work will uncover links between lysosomes and immune responses that may apply to many other neurodegenerative conditions