STXBP5L (syntaxin binding protein 5-like), located on chromosome 3.33, is a SNARE-domain-containing protein that regulates vesicle trafficking and exocytosis 1. The protein inhibits exocytosis by interfering with SNARE complex formation between secretory vesicles and the plasma membrane 2. In pancreatic beta-cells, STXBP5L suppresses insulin secretion through interactions with syntaxin proteins (STX1A and STX4) that mediate insulin granule fusion 3. In neurons, STXBP5L inhibits synaptic vesicle fusion and neurotransmitter release, though recent evidence suggests it also influences dense core vesicle biogenesis and cargo composition rather than solely blocking exocytosis 4. STXBP5L promotes axonal outgrowth, with disease-associated variants impairing this function 2. Clinically, STXBP5L mutations cause infantile-onset neurodegenerative disease featuring sensorimotor neuropathy, optic atrophy, and cognitive deficits; pathogenic variants enhance exocytosis inhibition 2. STXBP5L variants associate with platelet secretion defects 5, term prelabor rupture of membranes 6, and hepatocellular carcinoma risk in cirrhotic patients 7. Elevated circular STXBP5L expression appears enriched in small-cell lung cancer, suggesting involvement in cancer pathogenesis 8.