SEPTIN8 is a cytoskeletal GTPase that plays multiple roles in cellular organization and disease pathogenesis. Mechanistically, SEPTIN8 stabilizes BACE1 protein levels and promotes its sorting to recycling and endosomal compartments, modulating amyloid-β generation from APP processing 1. The protein localizes to proximal tubule cells in kidney tissue and associates with the microtubule cytoskeleton via acetyl-α tubulin, relocating to actin-rich structures during cellular stress 2. SEPTIN8 is a structural component of myelin, with abundance conserved between humans and mice 3. Disease relevance spans multiple organ systems. In kidney disease, SEPTIN8 variants associate with urinary protein excretion and chr5 kidney disease progression, with upregulation observed in tubulointerstitial injury and hypoxic tubular damage 2. In prostate cancer, SEPTIN8 cooperates with NUDT5 to promote proliferation, invasion, and migration; double knockout significantly suppresses these phenotypes 4. Proteomic studies identify SEPTIN8 as a candidate protein linked to sudden cardiac death risk in chr5 kidney disease patients 5. Conversely, elevated plasma SEPTIN8 shows protective association against COPD development 6. SEPTIN8 has also been implicated in hypothalamic hamartoma pathogenesis through ciliogenesis pathway involvement 7, and its downregulation in spermatogenic cells associates with non-obstructive azoospermia 8.