By integrating human lung samples, multi‐omics analyses, animal models, and mechanistic in vitro studies, it is revealed that how neutrophil–endothelial interactions mediated through the S100A9‐RAGE‐PI3K‐AKT signaling pathway contribute to endothelial dysfunction and vascular remodeling in PH. The gene discussed is AKT1; the disease is endothelial dysfunction.