Septin-5 (SEPT5)

Septin-5 (SEPT5), also known as CDCrel-1, is a filament-forming cytoskeletal GTPase that belongs to the highly conserved septin family. It is predominantly expressed in the central nervous system, heart, and platelets, where it functions as a molecular scaffold to regulate critical cellular processes such as cytokinesis, vesicle trafficking, and exocytosis [2, 7]. In the brain, Septin-5 localizes to presynaptic terminals and interacts with syntaxin-1 to modulate the release of neurotransmitters, making it a key player in synaptic plasticity and neuronal homeostasis [9, 11]. Pathologically, Septin-5 is a substrate of the E3 ubiquitin ligase parkin; its failure to be degraded leads to toxic accumulation in early-onset Parkinson's disease [7, 17]. Additionally, the SEPT5 gene is located in the 22q11.2 chromosomal region frequently deleted in DiGeorge syndrome, and it is involved in oncogenic translocations in acute myeloid leukemia [1, 5]. Recent research highlights Septin-5 as a potential therapeutic target in cancer, where inhibiting its assembly can disrupt pro-survival signaling hubs [6].

Other names

CDCrel-1Cell division control-related protein 1CDCREL1PNUTL1H5Peanut-like protein 1SEPTIN5

Small molecule inhibition of septin assembly and polymer formation to disrupt scaffolding for oncogenic signaling hubs or regulate synaptic vesicle exocytosis.