In parallel, the mini-review by Chen et al. frames NLRP3 as a critical downstream effector of the cGAS–STING (cyclic GMP-AMP synthase- stimulator of interferon genes) cytosolic DNA-sensing pathway, which links mitochondrial damage and misplaced DNA to type I interferon responses, inflammasome activation, pyroptosis, and chronic inflammation across neurodegenerative, cardiovascular, hepatic, and renal diseases. Here, CGAS is linked to kidney disorder.