The transcriptional regulation of all septins is complex, resulting in alternatively spliced variants. At least three septins (Septin 1, 2 and 4) are associated with a Tau-based paired helical filament core and may contribute to the formation of neurofibrillary tangle as integral constituents of paired helical filaments. Septin 3 (G-Septin), a GTPbinding protein, is highly expressed in brain and is regulated by protein kinase G in neurons. The human SEPT4 (H5/PNUTL2/CDCrREL-2) gene encodes ARTS (for apoptosis-related protein in the TGF ? signaling pathway), which is expressed in many cells and acts to enhance cell death induced by TGF ? or, to a lesser extent, by other apoptotic agents. ARTS is localized to mitochondria and translocates to the nucleus when apoptosis occurs.