In conclusion, our findings advance understanding of SP-C maturation by identifying a previously uncharacterized early proteolytic processing step shown to be essential to exclude aberrant transport of the proprotein to the plasma membrane, refining the model of SP-C trafficking, and highlighting the intricate regulation of protein processing in the Golgi – opening new avenues for investigating how misprocessing of SP-C might contribute to diseases such as idiopathic pulmonary fibrosis (IPF). This evidence concerns the gene SFTPC and pulmonary fibrosis.