Vnn1, also known as Vanin1, is an exogenous enzyme with pantetheinase activity. It degrades pantetheine to pantothenate (vitamin B5, a precursor of coenzyme A (CoA) biosynthesis) and cysteamine, playing a role in multiple metabolic pathways such as glucolipid metabolism, cysteamine metabolism, and glutathione metabolism [3,4].

In colitis, VNN1 overexpression on colonocytes correlates with IBD severity. The VIVA mouse model, which overexpresses Vnn1 on intestinal epithelial cells, is resistant to experimentally induced colitis. Vnn1's pantetheinase activity enhances CoA regeneration and metabolic adaptation of colonocytes, favors microbiota-dependent production of short-chain fatty acids (especially butyrate), and is a compensatory mechanism to reinforce the mucosal barrier [1].

In acute pancreatitis, pancreatic ductal deletion of S100A9 alleviates the condition by targeting VNN1-mediated ROS release to inhibit NLRP3 activation [2].

In the AKI-CKD transition, VNN1 knockout mice show accelerated recovery of renal function and inhibited renal fibrosis after ischemia/reperfusion injury, with suppressed senescence of renal tubular cells, suggesting VNN1 promotes the transition via inducing cellular senescence by affecting RB1 expression [5].

In conclusion, Vnn1 is crucial in various biological processes and disease conditions. Studies using gene knockout mouse models have revealed its role in colitis, acute pancreatitis, and the AKI-CKD transition. These findings contribute to understanding disease mechanisms and may offer potential therapeutic targets for related diseases.