The phosphatidylinositol transfer protein domain (PITP) is an evolutionarily conserved protein that is able to transfer phosphatidylinositol between membranes in vitro and in vivo. However some animal genomes also include genes that encode proteins where the PITP is found in cis with a number of additional domains and recent large scale genome sequencing efforts indicate that this type of multidomain architecture is widespread in the animal kingdom. In Drosophila photoreceptors, the multidomain phosphatidylinositol transfer protein RDGB is required to regulate phosphoinositide turnover during G-protein activated phospholipase C signalling. Recent studies in flies and mammalian cell culture models have begun to elucidate functions for the non-PITP of RDGB and its vertebrate orthologs. We review emerging evidence on the genomics, functional and cell biological perspectives of these multi-domain PITP containing proteins.