Background: Disruption to regulation of nuclear factor-kappa beta (NF-κB) has been associated with a number of inflammatory conditions including atherosclerosis. The protein A20-binding inhibitor (ABIN) has a polyubiquitin binding domain homologous to that present in NF-κB essential modulator (NEMO), a key component of the inhibitor NF-κB (IκB) kinase (IKK) complex. Mice bearing a mutation in ABIN-1 [D485N] produce numerous physiological changes typical of autoimmunity. Remodelling of the vascular wall and invasion of mononuclear cells has previously been reported, although the functional consequences of this are yet to be established. Aim: To better understand the relationship between ABIN-1 protein mutation and vascular function in an in vivo mouse model. Method: Skin microcirculation was assessed on the flanks of anesthetised (1.5-2% isoflurane with oxygen) C57BL/3 ABIN-1 knock-in (KI) (n=17) and wild-type (WT) (n=17) mice aged 12-18 weeks. Laser Doppler Imaging (LDI) with drug iontophoresis of phenlepherine (PE), acetylcholine (ACh), sodium nitroprusside (SNP), and localised skin heating (45°C) were used to measure vascular function. Results are expressed as mean percentage change in perfusion (maximum response-baseline) ± standard error of mean (SEM). Additionally, skin fluorescence measurements in arbitrary units (AU) ±SEM were made to quantify levels of NADH, flavins, pyridoxine and carotene. One-way ANOVA and T-test analysis were used for statistical significance (p<0.05). Results: Significant differences between ACh induced vasodilation in KI (change in skin perfusion 23±3%) and WT (change in skin perfusion 34±3%) mice were observed (p =0.007). No significant differences were noted for SNP (KI change in skin perfusion 35±4%, WT change in perfusion 31±3%) or for localised skin heating (KI change in skin perfusion 40±3%, WT change in perfusion 40±4%). Significant differences for pyridoxine (KI 197±15AU, WT 243±10AU) were evident (p =0.037). No significant changes were observed for NADH (KI 314±47AU, WT 396±4AU), flavins (KI 320±64AU, WT 400±17AU), or carotene (KI 169±6AU, WT 188±7AU). Conclusion: ACh induced vasodilation was significantly reduced in KI mice. However maximal dilatory capacity as tested by SNP and localised skin heating were not significantly different between groups, suggesting localised damage to the endothelium. A reduction in pyridoxine, an existing independent risk factor for vascular disease, might be one factor responsible for this dysfunction. The exact cellular consequences and resulting physiology of this interaction requires further scrutiny.