NEFH encodes the neurofilament heavy chain protein, a critical structural component of intermediate filaments in mature neurons. NEFH functions primarily in maintaining axonal caliber and supporting neuronal architecture, working in cooperation with other neurofilament proteins NEFL and NEFM 1. The protein is essential for proper axonal development and forms three-dimensional lattices that organize cytoplasmic organelles within axons 1. NEFH expression must be tightly regulated, as dysregulated stoichiometry of neurofilament proteins leads to pathological neuronal cytoplasmic inclusions and axonal degeneration 1. The gene serves as a reliable biomarker for neuronal damage, with elevated NEFH levels detected in plasma of amyotrophic lateral sclerosis (ALS) patients, correlating with disease progression and survival outcomes 23. In ALS patients with NEFH mutations, reduced brain glucose metabolism in cortex-striatum circuits correlates with motor dysfunction and serves as an independent prognostic factor 3. The NEFH promoter demonstrates high selectivity for retinal ganglion cells, making it valuable for targeted gene therapy applications 4. Beyond neurological contexts, NEFH functions as a tumor suppressor in prostate cancer, where its downregulation promotes castration-resistant growth and metastasis 56.