Furthermore, mechanistically, our study showed that pharmacological inhibition of mPTP opening by CsA blocked the release of mtDNA into the cytosol, and pharmacological inhibition of TLR9 activation by E6446 blocked TLR9 recognition and binding of mtDNA, both of which blocked the activation of the TLR9-NF-κB-NLRP3 axis and mitigated NPC pyroptosis in vitro and the development of IVDD in vivo (Fig. 8). Here, NFKB1 is linked to nasopharyngeal carcinoma.