Inhibition of EMC3/EMC or VCP in SftpcI73T transgenic mice and in SFTPCI73T iAT2 cells improved mitochondrial dysfunction in association with changes in protein transport without affecting normal AT2 cell function in neonatal or adult mice, supporting potential targeting of EMC3 and VCP pathways for development of treatments to prevent or treat SFTPCI73T-related ILD. Here, VCP is linked to interstitial lung disease.