FUS/TLS, one of causative gene for familial ALS (fALS), encodes a multifunctional DNA/RNA binding protein. FUS/TLS, continuously nucleo-cytoplasmic shuttling, contains an N-terminal QGSY (Gln-Gly-Ser-Tyr)-rich region, a Glycine-rich region, an RRM (RNA recognition motif), two RGG (Arg-Gly-Gly ) repeats divided by a zinc finger motif, and a highly conserved C-terminal non-classical NLS (nuclear localization signal) recognized by nuclear transporter transportin. A variety of fALS-linked mutations are clustered in the C-terminal NLS, which impairs the interaction between NLS and import receptor transportin resulting in the cytoplasmic mislocalization. Since arginine methylation is implicated in the subcellular localization of FUS/TLS, we examined the effect of methylation inhibitors on the subcellular localization of ALS-linked mutant FUS P525L. The treatment with global methylation inhibitor AdOx (adenosine dialdehyde) remarkably reuduced the cytosoplasmic mislocalization of FUS/TLS. The pull down assay demonstrated the binding of FUS/TLS with transprotin was potentiated by the treatment with AdOx. The deletion of RGG domains abolished the effect of AdOx, which suggests the arginine methylation in RGG domains might be essential for AdOx treatment to modulate the binding to transportin.