Vnn3, also known as vanin-3, is a member of the pantetheinase gene family. Pantetheinase enzymes hydrolyze pantetheine into pantothenic acid (vitamin B5) and cysteamine, with cysteamine being a key regulator of host responses to inflammatory stimuli. Vanin genes are clustered (human 6q22-24 and mouse 10A2B1) and Vnn3 is thought to have functions related to neutrophil regulation, response to oxidative stress, and may be involved in tissue repair processes related to oxidative stress [3,4].

In clear cell renal cell carcinoma (ccRCC), VNN3 expression was considerably higher in stages III and IV than in stages I and II. High VNN3 expression was associated with poor prognoses, suggesting it could be used as a biomarker to predict ccRCC prognosis [1]. In benzene-exposed workers, there was a remarkable correlation between VNN3 expression and hemogram. In vitro, 1,4-benzoquinone (a benzene metabolite) increased VNN3 expression, inhibited cell proliferation, and regulated the expression of KLF15 and NOTCH1 related to cell proliferation, with VNN3 influencing these processes. This indicates VNN3 may be a biomarker of benzene toxicity [2]. Mice defective in the enzyme pantetheinase (Vnn3) show increased susceptibility to blood-stage malaria (increased parasitaemia, reduced survival), and cysteamine (the reaction product of pantetheinase) supplementation corrects in part the malaria-susceptibility phenotype of the mutants [5].

In conclusion, Vnn3 is involved in multiple biological processes. Its role in disease is significant, such as in ccRCC prognosis prediction, benzene toxicity indication, and malaria susceptibility regulation. Studies on Vnn3-defective mouse models have provided insights into its functions in these disease-related areas, highlighting its potential as a biomarker and a target for further research in these disease conditions.