TIFA and retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome: By leveraging mechanistic cellular models alongside clinical phenotyping of ROSAH syndrome, a monogenic autoinflammatory disorder driven by activating ALPK1 mutations, we establish that ALPK1 activation amplifies STING signaling, while STING activation reciprocally modulates ALPK1/TIFA/NF-κB signaling.