Precision tuning of STING signaling: a mutational blueprint

In a recent publication in Nature , Zhang et al. present a comprehensive functional atlas of stimulator of interferon genes (STING), a central adaptor of innate immunity. 1 By systematically interrogating thousands of single amino-acid substitutions, the study reveals how distinct structural regions of STING collectively regulate interferon induction, NF-κB activation and non-canonical autophagy. The work provides a new molecular framework for understanding STING activation, disease-associated variants and future therapeutic modulation of this pathway.