NEFM (neurofilament medium chain) is a major cytoskeletal protein that forms part of the neurofilament triad alongside NEFL and NEFH, functioning to determine axonal caliber, promote axonal growth, and organize cytoplasmic organelles within myelinated axons 1. NEFM maintains structural integrity of the neuronal cytoskeleton and participates in neurofilament bundle assembly through protein-protein interactions 1. In pathological contexts, dysregulated NEFM expression contributes to multiple neurodegenerative conditions. In amyotrophic lateral sclerosis (ALS), altered stoichiometry of neurofilament subunits—driven by dysregulated ALS-linked miRNAs that suppress NEFM transcript levels—leads to neuronal cytoplasmic inclusions and axonal degeneration 1. NEFM variants affecting phosphorylation have been identified in hereditary cerebellar ataxia, where neurofilament aggregation correlates with neurodegeneration 2. In progressive supranuclear palsy, reduced NEFM levels in cerebrospinal fluid serve as a potential biomarker distinguishing the disease from Parkinson's disease and healthy controls 3. Additionally, NEFM upregulation occurs in thyroid eye disease orbital tissues, contributing to nerve injury pathology 4. Clinically, NEFM shows promise as a diagnostic and prognostic biomarker. High NEFM expression correlates with improved overall and recurrence-free survival in breast cancer, with expression positively associating with immune infiltration 5. NEFM also functions as a key diagnostic biomarker for periodontitis in machine learning-based frameworks 6, and neuroprotective interventions can upregulate NEFM expression to promote neuronal health 7.