GFAP is a 50 kDa intracytoplasmic filamentous protein that constitutes a portion of the cytoskeleton in astrocytes, and it has proved to be the most specific marker for cells of astrocytic origin. In the central rod domain of the molecule, GFAP shares considerable structural homology with the other intermediate filaments. Functionally, GFAP is thought to be important in astrocyte motility and shape by providing structural stability to astrocytic processes. Following injury to the human CNS caused by trauma, genetic disorders, or chemicals, astrocytes proliferate and show extensive hypertrophy of the cell body and processes, and GFAP is markedly upregulated. In contrast with increasing astrocyte malignancy, there is a progressive loss of GFAP production. Thus, malignant astrocytomas have fewer tumor cells that stain positively and intensely for GFAP than do less malignant astocytomas and normal brain specimens. Outside the CNS, sensitive detection methods may demonstrate GFAP in Schwann cells, enteric glia cells, salivary gland neoplasms, and metastasizing renal carcinomas. Additionally, GFAP immunoreactivity has been demonstrated in epiglottic cartilage, pituicytes, immature oligodendrocytes, papillary meningiomas, and myoepithelial cells of the breast.