•Development of a new protocol for the separation of positive cytoplasmic granules.•The mutant FUS in fibroblast cell line derived from ALS's and can interfere with the translation process.•The mutant FUS interfered with the automatic regulation of NMD and increased its activity by increasing its promoting factors (UPF1, UPF3b) and decreasing its negative regulatory factors (UPF3a). Here, UPF3B is linked to amyotrophic lateral sclerosis.