Amyotrophic lateral sclerosis (ALS)is a neurodegenerative disease that currently has no effective treatment, and its pathogenesis is unclear. Recent studies have found that transactive response element DNA binding protein-43 (TDP-43) plays an important role in neurodegenerative diseases including ALS and frontotemporal dementia. This article summarizes the latest understanding of the structure of TDP-43 in the past decade, its role in the pathogenesis of neurodegenerative diseases, and potential therapeutic targets, in order to provide a basic research basis for the integrated diagnosis and treatment of ALS with Chinese and Western medicine.