Methodological caveats regarding "Novel insights into surfactant protein C trafficking revealed through the study of a pathogenic mutant"

We read with great interest the paper by Dickens, et al . entitled “Novel insights into surfactant protein C trafficking revealed through the study of a pathogenic mutant ” recently published in ERJ (DOI: 10.1183/13993003.00267-2021). This in vitro study examined biosynthetic trafficking of SP-C ( SFTPCWT ) and a clinical missense SFTPC mutant (Ile -> Thr at codon 73) associated with interstitial lung disease, SFTPCI73T [4]. Consistent with prior studies in other cell lines [3, 9, 14], an in vivo mouse model [13], human induced Pleuripotent Stem Cell (iPSC) derived alveolar type 2 (AT2) cells [1], and patient samples [4, 9], the authors demonstrate an aberrant distribution of SP-CI73T proprotein on the plasma membrane (PM) of their model system as well on AT2 cells from SFTPCI73T mice. Interestingly, they show that a previously recognised increase in apparent molecular weight (Mr) of mutant SFTPCI73T is due to post-translational glycosylation presumably on Thr-73, as a SFTPCI73A construct was incapable of supporting glycosylation but also mislocalized to PM. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr. Beers reports grants from National Institutes of Health U01 HL152970, United States Department of Veterans Affairs, Bristol Meyers Squibb, Inc, Optikira, LLC; License (SftpcI73T Mouse) Payments to Institution from Galapagos, Inc, License (SftpcC121G Mouse) Payments to Both from BMS-Celgene; consulting fees from Boehringer-Ingelheim, Gilead Sciences, Inc; outside the submitted work. Conflict of interest: Dr. Mulugeta has nothing to disclose. Conflict of interest: Dr. Weaver has nothing to disclose.