Disease-associated ALPK1 variants are principally implicated in two human pathologies: Thr237Met and Tyr254Cys alterations are mechanistically connected to ROSAH syndrome, while the Val1092Ala substitution constitutes 45% of spiradenoma and 30% of spiradenocarcinoma occurrences within analyzed clinical cohorts (20). Here, ALPK1 is linked to retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome.