Syntaxin-17, a vital autophagosome‒lysosome fusion protein, serves as a potential biomarker of spinal cord injury severity

Traumatic spinal cord injuries (SCIs) exhibit marked differences in severity, yet objective biomarkers reflecting early pathological status remain limited. Here, we identify syntaxin-17 (STX17), a key autophagosomal SNARE protein, as a severity-associated biomarker and functional regulator of autophagic flux following SCI. Proteomic profiling and experimental validation revealed that moderate SCI is characterized by increased autophagic flux accompanied by increased neuronal STX17 expression, whereas severe SCI is characterized by STX17 downregulation, impaired autophagosome–lysosome fusion, and exacerbated neuronal necroptosis. Notably, serum STX17 levels in both SCI patients and mouse models correlated with injury severity, highlighting its translational potential as a biomarker. Mechanistically, restoring STX17 expression reestablished autophagic flux, suppressed necroptosis, and promoted axonal regeneration and functional recovery after severe SCI. We further identified an upstream circRNA–miRNA regulatory mechanism that modulates STX17 expression in neurons. Collectively, our findings establish STX17 as a previously unrecognized biomarker and therapeutic target that links autophagic flux dysregulation to injury severity and neuronal fate after traumatic SCI.