Huntington’s disease (HD) has conventionally been treated as a disease of the brain, specifically of the medium spiny neurons whose dysfunction and death is a characteristic feature of HD pathology, and which lead to the chorea associated with the disorder. However, the huntingtin protein is ubiquitously expressed, and increasingly HD is being appreciated as a whole body disorder. Indeed, one of the features of HD is the perturbation of the kynurenine pathway of tryptophan degradation, which can be detected in blood samples drawn from the periphery. In Humans, kynurenine can be broken down into both the neurotoxic free radical generator 3-hydroxykynurenine (3-HK), and the neuroprotective free radical scavenger kynurenic acid (KYNA). In HD patients the balance of this synthesis is shifted such that much more 3-HK is produced – a process we have recently shown to play a key role in HD mediated neurodegeneration (Campesan et al., 2011). Recent work in R6/2 HD model mice found that pharmacological inhibition of the KMO enzyme responsible for 3-HK synthesis using the prodrug JM6 was significantly neuroprotective, despite the JM6 compound not crossing the blood brain barrier (Zwilling et al., 2011). In this paper, Zwilling et. al. propose a model in which the action of JM6 leads to elevated levels of kynurenine in the blood, which is then actively transported into the brain, stimulating increased formation of neuroprotective KYNA in astrocytes. Our research therefore seeks to augment HD therapeutics targeting the kynurenine pathway by identifying transporters responsible for the active transport of kynurenine, building on the identification LAT1 as a tryptophan/kynurenine exchanger (Kaper et al., 2007). To address this we work in Drosophila, which utilise kynurenine pathway metabolites to synthesise brown pigments called ommochromes, which are deposited as UV filters in the eyes. Mutations affecting both the synthesis and transport of kynurenine pathway metabolites therefore manifest as changes in eye colour due to changes in ommochrome levels, and to date over 85 such mutants have been found (Lloyd et al., 1998). We have recently mapped a series of these classical eye colour mutants to the Drosophila genome sequence using standard genetic techniques, uncovering new catalytic enzymes and transporters acting in the kynurenine pathway. We are currently characterising the role of these genes in detail, with particular emphasis on their potential for augmenting the action of JM6 in the treatment of HD.