Phytochromes are light responsive photoreceptors in plants that influence development and differentiation during the entire plant life cycle. Plant nucleoside diphosphate kinase 2 (NDPK2) has been reported to be a component of the light-mediated signalling cascade and to interact physically with phytochrome A in the cytosol. By using diverse methods as in vitro imports, in vivo localisation of GFP-fusion proteins and immuno blotting of plant cell fractions we clearly localise NDPK2 only to chloroplasts but not to the cytosol, demonstrating that although high affinity protein-protein interactions can occur in vitro, their physiological relevance can be artificial if the proteins are localised to different cell compartments in vivo.