Recent studies point to an important role of RAGE in the pulmonary compartment in physiological as well as in pathological circumstances. Physiologically, RAGE is expressed at high basal levels in the lungs relative to other tissues [26, [29] [30] [31] [32] [33] [34] , suggesting that RAGE may have lung-specifi c functions distinct from the role of RAGE in other adult tissues. In particular, although the kidney is dramatically aff ected by microangiopathy and fi brosiswhich is substantially attributed to RAGE -in patients with diabetes, the lungs, with a signifi cantly higher baseline RAGE expression than the kidney, remain unaff ected. In addition, RAGE has been found to be specifi cally localized near the basal cell membrane within alveolar pneumocytes [32, 35, 36] . Th ese two observa tions raise the question as to whether RAGE has a function in normal healthy lungs. Indeed, Englert et al. documented that aged RAGE -/mice develop pulmonary fi brosis-like alterations spontaneously; lungs from 19 to 24 month-old RAGE -/mice showed increased collagen staining and displayed increased levels of hydroxyproline relative to wild type mice [31] . RAGE knockdown in pulmonary fi broblasts increased their proliferation and migration in vitro, suggesting an important protective function of RAGE in the lungs and that loss of RAGE may be related to functional changes of pulmonary cell types resulting in fi brotic disease [34] . Another study demonstrated that RAGE on epithelial cells promoted their adherence to human collagen (a major component of the alveolar basal lamina) and a spreading morphology, which may facilitate gas exchange and alveolar stability in vivo [34, 35] . Together, these data suggest that RAGE plays a role in maintaining lung homeostasis in normal, healthy lungs. Further studies are needed to unravel the function(s) of pulmonary RAGE in physiology in more detail.