Using U937 cell lines to model monocytes expressing various ALPK1 variants, we observed that IFN-γ is promoting IL-8 release specifically in cells expressing either one of the two ROSAH variants (p.T237M or p.Y254C) or in cells expressing the recurrent spiradenoma variant (p.V1092A), suggesting that IFN-γ can functionally promote expression of the pathogenic trait. Here, ALPK1 is linked to benign spiradenoma.