Therefore, in this study we compared the functional impact of TDP-43 ALS-linked LCD mutations located within IDR1, IDR2, or near the conserved helical region on TDP-43 RNP transport, and we performed a mutagenesis study of structural elements, aromatic, and charged residues in the LCD to identify key determinants of TDP-43 RNP transport in neurons. Here, RNPC3 is linked to amyotrophic lateral sclerosis.