Even though precise mechanisms on how NEFH regulates b-catenin are still needs to be further elucidated, epigenetic silencing of the NEFH gene in ESCC seems to be responsible for increased β-catenin expression, leading to activation of β-catenin/TCF-dependent transcription and key downstream effectors, leading to ESCC tumorigenesis. Here, NEFH is linked to esophageal squamous cell carcinoma.