Deficiency of the extracellular matrix (ECM) protein latent transforming growth factor beta (TGFβ) binding protein 4 (LTBP-4) results in lack of intact elastic fibers, which leads to disturbed pulmonary development and lack of normal alveolarization in humans and mice. Formation of alveoli and alveolar septation in pulmonary development requires the concerted interaction of extracellular matrix proteins, growth factors like TGFβ, fibroblasts and myofibroblasts to promote elastogenesis as well as vascular formation in the alveolar septae. To investigate the role of LTBP-4 in this context, lungs of LTBP-4 deficient (Ltbp4-/-) mice were analyzed in close detail. We elucidate the role of LTBP-4 in pulmonary alveolarization and show that three different, interacting mechanisms might contribute to alveolar septation defects in Ltbp4-/- lungs, i) absence of an intact elastic fiber network, ii) reduced angiogenesis and iii) upregulation of TGFβ activity resulting in profibrotic processes in the lung.