Hgfac, short for hepatocyte growth factor activator, is a serine endopeptidase. It circulates in plasma as a zymogen (proHGFAC), and once activated, it cleaves proHGF at Arg494-Val495 to form the active heterodimer HGF, thus initiating HGF-induced MET signaling. This process is crucial for tissue regeneration and repair as HGF has important roles in the regeneration of injured tissues. Macrophage stimulating protein, a ligand of RON, is also activated by HGFAC in vivo [2].

In genetic mouse models, Hgfac knockout (KO) led to significant phenotypes. Female Hgfac KO mice showed decreased chronic alcohol consumption and preference, while male Hgfac KO mice had decreased nicotine preference. This indicates a role for Hgfac in alcohol and tobacco use in a sex-specific manner [3]. In the context of Crohn's disease, the risk variant HGFAC R509H disrupted a damage-sensing pathway, impaired the activation of macrophage-stimulating protein, and led to impaired wound-associated epithelial cell induction and delayed healing in Hgfac R509H mice [1].

In conclusion, Hgfac is essential for activating growth factors like HGF, which is vital for tissue repair. The study of Hgfac KO mouse models has revealed its role in alcohol and nicotine consumption as well as in the pathophysiology of Crohn's disease, providing valuable insights into these biological processes and disease conditions.