The NS1 binding protein, known for interacting with the influenza A virus protein, is involved in RNA processing, cancer, and nerve cell growth regulation. However, its role in stress response independent of viral infections remains unclear. This study investigates the function of NS1 binding protein in regulating stress granules during oxidative stress through interactions with GABARAP subfamily proteins. We find that NS1 binding protein localizes to stress granules, interacting with core components, GABARAP proteins, and p62, a protein involved in autophagy. In cells lacking NS1 binding protein, stress granule dynamics are altered and p62 ubiquitination is increased, suggesting impaired stress granule degradation. Overexpression of NS1 binding protein reduces p62 ubiquitination. In neurons derived from patients with amyotrophic lateral sclerosis (ALS). reduced levels of NS1 binding protein and p62 disrupt stress granule morphology. Recently, we performed LC-MS/MS-based proteomic analysis to identify NS1 binding protein-interacting partners and discovered additional candidates involved in stress granule dynamics and autophagy regulation. These findings identify NS1 binding protein as a negative regulator of p62 ubiquitination and a facilitator of GABARAP recruitment to stress granules, implicating it in stress granule regulation and the pathogenesis of ALS.