SNF8 is a core component of the ESCRT-II complex essential for membrane trafficking and cellular homeostasis. Functionally, SNF8 mediates multivesicular body (MVB) formation and endosomal cargo sorting for lysosomal degradation 1, particularly of transmembrane proteins like EGFR and CXCR4. Beyond canonical ESCRT functions, SNF8 participates in exosomal cargo sorting, enabling release of proteins including CD63 and syndecan 2, and regulates TRPC6 ion channel activity through direct protein-protein interaction 3. SNF8 also functions in the nucleus as a transcriptional co-regulator, interacting with IRF3 and CBP to promote type I/III interferon responses during antiviral defense 4, and modulates DAF-16-dependent longevity pathways 5. Clinically, bi-allelic SNF8 variants cause a severe neurodevelopmental spectrum: loss-of-function mutations produce devastating developmental and epileptic encephalopathy with massive white matter reduction and early death, while hypomorphic variants (p.Val102Ile) result in milder phenotypes including intellectual disability and optic atrophy 1. Disease mechanisms primarily involve impaired autophagy and ESCRT-II complex dysfunction, validated in zebrafish models showing developmental delay and optic nerve impairment. These findings establish SNF8 as a multifunctional hub integrating membrane trafficking, transcriptional regulation, and cellular stress responses critical for neurological development.