Surfactant proteins (SFTPs) are trafficked from the ER membrane to lamellar bodies (LBs) via the multi-vesicle body (MVB). The pro-SFTPs B and C are cleaved here to produce functional SFTPs. Defects in the SFTPC gene result in protein misfolding, misrouting and/or misprocessing resulting in accumulation of partially-processed, inactive pro-SFTPC in alveoli causing cell toxicity. Defects in SFTPC can cause pulmonary surfactant metabolism dysfunction 2 (SMDP2; MIM:610913), a rare lung disorder due to impaired surfactant homeostasis characterised by alveoli filling with floccular material. Cellular responses to the misfolded pro-SFTPC products include ER stress, the activation of reactive oxygen species and autophagy. Excessive lipoprotein accumulation in the alveoli results in a form of respiratory distress syndrome in premature infants (RDS; MIM:267450). Mutations causing RDS that arrest the pro-protein in the ER include P30L and P115L (Thurm et al. 2013).