Revealing VNN1: An Emerging and Promising Target for Inflammation and Redox Balance

Abstract

Introduction: The intricate balance between immunometabolic homeostasis and redox equilibrium is crucial for maintaining health, and its dysregulation is implicated in a wide spectrum of diseases. Vascular non-inflammatory molecule-1 (VNN1) is an emerging pantetheinase that sits at the crossroads of inflammation and metabolism, yet a comprehensive review that synthesizes its tissue- and disease-specific roles and systematically evaluates its potential as a therapeutic target remains lacking. Methods: A systematic literature search was conducted to identify relevant domestic and international studies on VNN1. The search included databases such as PubMed using keywords related to VNN1′s structure and function, the disease roles of its metabolites (pantothenic acid, cysteamine), or inhibitors efficacy. The selected studies were critically reviewed and summarized to extract key pathways, inhibitor profiles and molecular docking analyses synthesized. Results: VNN1 hydrolyzes pantetheine to generate metabolites essential for CoA synthesis and glutathione redox balance. Its upregulation is closely associated with the pathogenesis of acute and chronic inflammatory diseases and certain cancers, often serving as a biomarker for disease severity. Inhibiting VNN1, either genetically or pharmacologically with compounds like RR6, OMP-7, or natural products such as oleuropein, demonstrates significant anti-inflammatory and antioxidant effects in preclinical models. Conclusions: VNN1 represents a promising therapeutic target for modulating oxidative stress and immunometabolism in various diseases. Future research should develop disease-specific inhibitors, clarify tissue-specific mechanisms, and conduct clinical trials for translation.