The Role of the Protease PCSK6 in Pathophysiology and Its Potential Role in Pulmonary Fibrosis

Proprotein convertase subtilisin/kexin type 6 (PCSK6) is a proteolytic enzyme that acts on a broad spectrum of substrates, including growth factors, extracellular proteases, adhesion molecules, protease activated receptor 1, the prorenin receptor, and Corin. As a consequence of its broad spectrum substrate activity, PCSK6 is implicated in a wide range of pathophysiological processes like cardiovascular disease, neurological disorders, arthritis and cancer. Of special interest, PCSK6 has recently been shown to be highly expressed in patients with idiopathic pulmonary fibrosis (IPF) and PCSK6 was associated with reduced survival, providing the first evidence linking PCSK6 to pulmonary fibrosis. In this review, we summarize the molecular biology of PCSK6, including its structural features and major substrates, and outline its pathophysiological roles across various diseases. Furthermore, we propose and discuss the potential involvement of PCSK6 in pulmonary fibrosis to guide future research.