Furin is a serine endoprotease that cleaves proprotein substrates in the secretory pathway, playing crucial roles in homeostasis and disease. It is essential for embryogenesis and activates a wide range of substrates, including growth factors, receptors, and extracellular matrix proteins. Furin's role in pathogenicity is significant, as it is involved in the activation of pathogens such as anthrax, influenza, and Ebola. Furin's cleavage site requirements have led to the development of inhibitors that block its activity in vitro and in vivo. Furin autoactivates through a multistep process involving its prodomain, which is cleaved in the endoplasmic reticulum and TGN/endosomal compartments. Furin localizes to the TGN and is involved in the trafficking of various proteins, including those involved in cell signaling and disease. Furin's role in the regulated secretory pathway is crucial for the maturation of secretory granules and the processing of proprotein substrates. Furin is also involved in the processing of neurotrophins, such as β-NGF, which can influence neuronal survival or death. Furin's role in Alzheimer's disease is linked to the processing of β-amyloid precursor protein (APP), which can lead to neurodegeneration. Furin is also involved in the activation of TNF family members and TGF-β family signaling, which are critical for development and disease. Furin's role in tumor metastasis is linked to the processing of matrix metalloproteinases and growth factors, which can promote cancer progression. Furin's involvement in viral pathogenesis is significant, as it is required for the activation of viral envelope glycoproteins, including those of HIV-1 and influenza. Furin's cleavage of viral proteins is essential for their fusogenic properties and virulence. The study of furin's trafficking and processing has provided insights into its roles in development, homeostasis, and disease, highlighting its importance as a key regulatory enzyme in cellular processes.Furin is a serine endoprotease that cleaves proprotein substrates in the secretory pathway, playing crucial roles in homeostasis and disease. It is essential for embryogenesis and activates a wide range of substrates, including growth factors, receptors, and extracellular matrix proteins. Furin's role in pathogenicity is significant, as it is involved in the activation of pathogens such as anthrax, influenza, and Ebola. Furin's cleavage site requirements have led to the development of inhibitors that block its activity in vitro and in vivo. Furin autoactivates through a multistep process involving its prodomain, which is cleaved in the endoplasmic reticulum and TGN/endosomal compartments. Furin localizes to the TGN and is involved in the trafficking of various proteins, including those involved in cell signaling and disease. Furin's role in the regulated secretory pathway is crucial for the maturation of secretory granules and the processing of proprotein substrates. Furin is also involved in the processing of neurotrophins, such as β-NGF, which can influence neuronal survival or death. Furin's role in Alzheimer's disease is linked to the processing of β-amyloid precursor protein (APP), which can lead to neurodegeneration. Furin is also involved in the activation of TNF family members and TGF-β family signaling, which are critical for development and disease. Furin's role in tumor metastasis is linked to the processing of matrix metalloproteinases and growth factors, which can promote cancer progression. Furin's involvement in viral pathogenesis is significant, as it is required for the activation of viral envelope glycoproteins, including those of HIV-1 and influenza. Furin's cleavage of viral proteins is essential for their fusogenic properties and virulence. The study of furin's trafficking and processing has provided insights into its roles in development, homeostasis, and disease, highlighting its importance as a key regulatory enzyme in cellular processes.