When a patient needs a lung transplant, chances are the donated organ will come from a person who suffered traumatic brain injury. Although the lungs of these donors seem intact, doctors have noticed that the organs are often leaky and inflamed. As a result, only 15 to 20% of the lungs are viable for transplant. To better understand why brain damage leads to lung damage, David S. Wilkes of Indiana University School of Medicine and coworkers focused on the small protein HMGB1. The team believes that brain injury triggers the release of HMGB1, which slips through the blood-brain barrier and travel to the lungs. There, the protein binds to a receptor known as RAGE, setting off an inflammatory response. The researchers tested their hypothesis by genetically engineering mice to lack RAGE and then inducing brain injuries in these rodents as well as in a group of otherwise healthy mice. The RAGE-less mice did not develop as much lung damage as the control group (Sci. Transl. Med. 2014, DOI: 10.1126/scitranslmed.3009443). The researchers also injected healthy mice with an antibody that deactivates HMGB1 just before giving the rodents a brain injury. These animals, too, sustained minimal lung damage.