Spermine synthase (SMS) is an X-linked aminopropyltransferase that catalyzes spermine production from spermidine and decarboxylated S-adenosylmethionine 1. The enzyme functions as an obligate dimer with a catalytic C-terminal domain and structurally distinct N-terminal and central domains 1. SMS plays a critical role in polyamine metabolism, which is vital for cellular and organismal function 2. Mutations in SMS cause Snyder-Robinson syndrome, an X-linked recessive intellectual developmental disorder characterized by mental retardation, skeletal defects, hypotonia, and movement disorders 1. Disease-causing mutations lead to spermidine accumulation and spermine reduction, resulting in autophagy blockage in the nervous system 2. Complete SMS loss impairs lysosomal function and blocks autophagic flux, while animal models demonstrate neurological abnormalities, sterility, deafness, and sudden death tendency 1. Emerging evidence reveals SMS reduction paradoxically enhances autophagy and suppresses tau accumulation in tauopathy models, suggesting partial SMS inhibition may represent a therapeutic approach for Alzheimer's disease 2. Postmortem Alzheimer's brain tissue shows modestly elevated SMS levels, establishing a functional correlation between polyamine metabolism and neurodegeneration 2. These findings identify SMS as a potential therapeutic target for neurodegenerative diseases beyond its established role in Snyder-Robinson syndrome pathogenesis.