A multitude of studies have underscored the DNA‐sensing cGAS‐STING pathway as a pivotal neuroinflammatory axis, integral to the pathogenesis of a spectrum of neurodegenerative diseases, such as PD, HD, AD, and ALS.[55] The nucleus‐derived cytoplasmic formation of chromatin fragments (CCFs) and activation of retrotransposons could activate the DNA‐sensing cGAS–STING pathway.[56] Here we demonstrated that damaged mtDNA triggered by disorders of lipid metabolism, not genomic DNA, activated this pathway, mediating the crosstalk between neurons and microglia in NDs. Here, CGAS is linked to amyotrophic lateral sclerosis.