The Dark Side of STING Signaling In Niemann‐Pick Disease Type C And Other Neurodegenerative Diseases

We found that NPC1 interacts with STING and recruits it to the lysosome for degradation in both human and mouse cells. Our findings also revealed that knockout of Npc1 'primes'STING signaling by physically linking or 'tethering' STING to SREBP2 trafficking. Loss of NPC1 protein also 'boosts' STING signaling by blocking lysosomal degradation. Both priming and boosting of STING signaling are required for severe neurological disease in the Npc1^-/- mouse CONCLUSION: Both priming and boosting of STING signaling are required for severe neurological disease in the Npc1^-/- mouse. This study provides a comprehensive understanding of the STING interactomes and its regulatory network, shedding light on potential therapeutic targets for neurological diseases.