The dual role of S100A8/A9 as potent inflammatory mediators, DAMP molecules, and sensitive biomarkers, combined with their strong translational relevance in conditions such as pulmonary hypertension and autoimmune diseases (87, 98, 99, 105, 106), underpins our emphasis on these proteins as the primary focus of this review. This evidence concerns the gene IGKV1D-22 and pulmonary arterial hypertension.