Furin-flox Mouse

Furin, the best-characterized member of the mammalian proprotein convertases, is a ubiquitously expressed single-pass type 1 transmembrane protein. It catalyzes the proteolytic maturation of a variety of prohormones and proproteins in the secretory pathway, thus regulating the maturation of numerous proproteins and being involved in various physiological and pathophysiological processes, from embryonic development to carcinogenesis [1,2].

Furin knockout is embryonically lethal, but its knockout in differentiated somatic cells is not. Cleavage of SARS-CoV-2 spike protein by furin promotes viral entry into lung cells, making furin an exciting therapeutic target for viral pathogens like SARS-CoV-2 [1]. In cancer, while some studies propose furin as a potential target for treating several human cancers as many of its regulated proproteins are involved in cancer hallmarks, other studies show that some types of cancer do not benefit from furin inhibition [2]. In cystic fibrosis airways, elevated furin levels contribute to disease pathogenesis, and its inhibition could be a therapeutic strategy [3]. In neurodegenerative and neuropsychiatric diseases, emerging evidence like reduced FURIN mRNA expression in patients' brains implicates its role, though its role in neurological diseases is still poorly understood compared to cancer and infectious diseases [4]. In type 2 diabetes, furin's role in relation to the mTOR signaling pathway is being explored [5]. For COVID-19, targeting furin could have clinical implications as it cleaves the S1/S2 site on SARS-CoV-2 spike protein, promoting viral transmission [6].

In conclusion, Furin is essential for the proteolytic maturation of various proproteins and is involved in multiple physiological and pathophysiological processes. The knowledge from furin-related gene knockout (KO) or conditional knockout (CKO) studies, where applicable, has provided insights into its role in diseases such as viral infections, cancer, cystic fibrosis, neurodegenerative and neuropsychiatric diseases, and potentially type 2 diabetes, highlighting its potential as a therapeutic target in these disease areas.