Human glial fibrillary acidic protein‐δ (GFAP‐δ) is a GFAP protein isoform that is encoded by an alternative splice variant of the GFAP‐gene. As a result, GFAP‐δ protein differs from the predominant splice form, GFAP‐α, by its C‐terminal protein sequence. In this study, we show that GFAP‐δ protein is not expressed by all GFAP‐expressing astrocytes but specifically by a subpopulation located in the subpial zone of the cerebral cortex, the subgranular zone of the hippocampus, and, most intensely, by a ribbon of astrocytes following the ependymal layer of the cerebral ventricles. Therefore, at least in the sub ventricular zone (SVZ), GFAP‐δ specifically marks the population of astrocytes that contain the neural stem cells in the adult human brain. Interestingly, the SVZ astrocytes actively splice GFAP‐δ transcripts, in contrast to astrocytes adjacent to this layer. Furthermore, we show that GFAP‐δ protein, unlike GFAP‐α, is not upregulated in astrogliosis. Our data therefore indicate a different functional role for GFAP‐δ in astrocyte physiology. Finally, transfection studies showed that GFAP‐δ protein expression has a negative effect on GFAP filament formation, and therefore could be important for modulating intermediate filament cytoskeletal properties, possibly facilitating astrocyte motility. Further studies on GFAP‐δ and the cells that express it are important for gaining insights into its function during differentiation, migration and during health and disease. © 2005 Wiley‐Liss, Inc.