cover the exposed basement membranes. In normal repair, the hyperplastic type II AECs die and the remaining cells spread and undergo a differentiation process to become type I AECs. Under pathologic conditions and in the presence of transforming growth factor beta (TGF-β), fibroblasts accumulate in these areas of damage and differentiate into myofibroblasts that secrete collagen and other proteins. In the current classification of the pathogenesis of IPF, it is believed that it occurs by way of the formation of a UIP (usual interstitial pneumonia) lesion, which then undergoes the aforementioned pathological condition characteristic of IPF. Other proposed repeated injury mechanisms indicate that IPF may result not just from a UIP lesion, but also from NSIP and DAD (nonspecific interstitial pneumonia and diffuse alveolar damage) lesions, or a combination of several. In the past, it was thought that inflammation was the first event in initiating lung tissue scarring. Later findings showed that the development of fibroblastic foci precedes the accumulation of inflammatory cells and the consequent deposition of collagen. This pathogenetic model is indirectly supported by the clinical features of IPF, including an insidious onset over several years, relatively infrequent acute exacerbations, and failure to respond to immunosuppressive therapy. However, it is the belief of some researchers that the disease is a multi-mechanistic one, wherein the trigger for the disease may stem from abnormalities in any number of wound healing pathways, including the inflammatory response. Such abnormalities could occur in any number of the nine implicated pathways (clotting cascade, antioxidant pathways, apoptosis, inflammatory cytokines, angiogenesis and vascular remodelling, growth factors, surfactant and matrix regulatory factors), and that through further investigation into all nine, novel therapies and approaches could be proposed on a unique or case-by-case basis should attempts at treating or circumventing complications in any one pathway prove unsuccessful. A number of therapies that target fibroblast activation or the synthesis of extracellular matrix are currently in early testing or are being considered for development. Familial IPF accounts for less than 5% of the total of patients with IPF and is clinically and histologically indistinguishable from sporadic IPF. Genetic associations include mutations in pulmonary surfactant proteins A1, A2, C (SFTPA1, SFTPA2B) and mucin (MUC5B). A remarkable aspect of the MUC5B variant is its high frequency of detection, as it is found in approximately 20% of individuals with Northern and Western European ancestry and in 19% of the Framingham Heart Study population.