Surfactant deficiency can be induced by a number of primitive and secondary mechanisms. Among them are genetic defects with mutations in SP-B gene (SFTPB) as well as genes coding for SP-C (SFTPC), ABCA3, and TTF-1 [41] [42] [43] . More than 30 SFTPB (located on chromosome 2) mutations have been identified among patients with a congenital deficiency in SP-B. For SFTPC located on chromosome 8, at least 35 mutations have been described, localized primarily in the COOHterminal Brichos domain [44, 45] . A proposed function of the Brichos domain is a chaperone-like activity, which could prevent misfolding and aggregation of the parent protein. Alterations in the Brichos domain could therefore lead to diseases through mechanisms related to abnormal protein processing and cell toxicity [46] . Recently, several studies have also documented the role of ABCA3 deficiency in ILD. ABCA3 functions in the transport of surfactant lipids into lamellar bodies and is required to maintain pulmonary surfactant phospholipid homeostasis. Another contributor of ILD is TTF-1 (NK2 homeobox 1) dysfunction. TTF-1 is a critical regulator of transcription for the surfactant protein SP-B and SP-C. It is encoded by a gene located on chromosome 14q13 and is composed of three exon and two introns [47] . It is expressed in the thyroid, brain and lung.