HK2-mediated augmentation of endothelial cell glycolysis promotes placental vascular disorders through lactylation and pyroptosis

• PE placentas exhibit coordinated upregulation of glycolysis, protein lactylation, and pyroptosis, linking metabolic dysregulation to inflammatory injury. • HK2 is identified as a central regulator of the glycolytic-lactylation-pyroptosis axis in placental endothelial cells, with silencing attenuating and overexpression exacerbating the pathological cascade. • Pharmacological glycolysis inhibition via 2-deoxyglucose reduces both lactylation and pyroptosis, suggesting a potential therapeutic strategy for PE. • The study reveals a novel mechanistic pathway in PE pathophysiology, offering new biomarkers and targets for diagnosis and intervention.