In the pulmonary system, the binding of extracellular HMGB1 to its receptor for advanced glycation end products (RAGE) activates the nuclear factor kappa light chain enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, leading to the upregulation of HMGB1 and other proinflammatory mediators and promoting the development of ARDS. The gene discussed is WNK2; the disease is acute respiratory distress syndrome.