In the present study, we have now uncovered a novel mechanism that PRMT5-mediated activation of NF-κB is dependent on signal-induced phosphorylation of PRMT5 at serine 15 (S15) and propose that blocking this posttranslational modification (PTM) could serve the dual purpose of impairing the tumor-associated functions of PRMT5 via attenuating its activity towards NF-κB as a potential treatment strategy for CRC [11,12]. Here, PRMT5 is linked to neoplasm.