| Septin 2 (SEPT2) is a filament-forming cytoskeletal GTPase of the mammalian septin family that assembles into hetero-oligomeric rods and filaments with other SEPT proteins, acting as a structural scaffold that organizes actin and microtubule networks, membrane diffusion barriers and mitotic machinery. The protein contains a conserved central GTP-binding domain flanked by an N‑terminal polybasic region that interacts with phosphoinositide-rich membranes and a C‑terminal coiled-coil segment that mediates higher-order assembly and association with partner septins and effector proteins. In interphase and dividing cells, SEPT2 participates in complexes such as SEPT2–SEPT6–SEPT7 that form filamentous structures along microtubules and at the cleavage furrow, contributing to cytokinesis, chromosome segregation and spindle organization; SEPT2 scaffolds at the midplane of the mitotic spindle are required to maintain the kinesin CENP‑E at kinetochores, support proper chromosome congression, and facilitate spindle elongation during anaphase. SEPT2 also regulates actin dynamics and vesicle trafficking: by maintaining polyglutamylated microtubules and impeding MAP4 binding to tubulin, it supports polarized columnar epithelial organization and efficient vesicle transport, and in polarized epithelia, SEPT2-dependent septin filaments contribute to cell shape and collective movements. At specialized membrane domains, SEPT2 forms part of diffusion barriers, notably at the base of primary cilia, where it helps assemble the tectonic/B9 complex and localizes the transmembrane protein TMEM231, thereby restricting lateral diffusion of membrane proteins between ciliary and plasma membranes and ensuring proper ciliogenesis and signaling. In the nervous system, septins, including SEPT2, participate in synaptic and neuronal architecture; septin filaments modulate dendritic spine morphology, axonal branching and trafficking, and accumulating evidence links septin dysregulation to synaptic dysfunction in neurodegenerative diseases, although SEPT2-specific roles are still being defined. In cancer, SEPT2 is overexpressed in several epithelial malignancies, including colorectal and ovarian cancer, and expression analyses show that SEPT2 levels correlate with clinicopathological parameters such as tumor stage, lymph node metastasis, and poor prognosis, suggesting a contribution to tumor growth and invasive behavior. SEPT2 influences proliferation, apoptosis and motility, likely through effects on cell division, cytoskeletal organization and membrane dynamics, and is increasingly positioned as a tumor-related gene and candidate biomarker within the broader class of septin “cancer critical” genes where altered expression and isoform balance, rather than recurrent point mutations, underpins oncogenic roles. |
