SNAP29 is a SNARE protein essential for autophagosome-lysosome fusion during autophagy. It forms critical SNARE complexes with STX17 and VAMP8 that drive membrane fusion between autophagosomes and lysosomes 1. SNAP29 participates in both STX17-SNAP29-VAMP8 and STX7-SNAP29-YKT6 complexes, with YKT6 forming a priming complex with STX17 and SNAP29 that enhances autophagy flux before being displaced by VAMP8 to form the fusogenic complex 1. The protein also contributes to mitochondria-lysosome contacts through the STX17-SNAP29-VAMP7 complex under hypoxic conditions 2. SNAP29 function can be regulated by post-translational modifications, including O-GlcNAcylation that excludes it from selective autophagy under non-starvation conditions 3. Disease relevance includes cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome, with variants in the 22q11.2 region affecting SNAP29 contributing to clinical phenotypes 4. Viral proteins can manipulate SNAP29 to promote infection, as demonstrated by SARS-CoV-2 ORF7a protein which activates caspase 3 to cleave SNAP29, impairing autophagosome-lysosome fusion and promoting viral replication 5.