PRMT5, also known as Hsl7, Jbp1, Skb1, Capsuleen, or Dart5, is the major protein arginine methyltransferase responsible for mono-and symmetric dimethylation of arginine. It plays critical roles in various normal cellular processes, regulating genome organization, transcription, stem cells, differentiation, the cell cycle, and spliceosome assembly through histone and other protein methylation. It is also involved in many regulatory pathways underlying cancer development, progression, and therapy-response [1,3].

PRMT5 dysregulation is implicated in multiple oncogenic processes. In high-risk neuroblastoma xenograft models, pharmacologic or genetic inhibition of PRMT5 abolishes AKT1 arginine 15 methylation, preventing AKT1 translocation and subsequent activation, which attenuates primary tumor growth and blocks metastasis. In MTAP-deleted cancers, depletion of PRMT5 impairs cell viability as MTAP-deleted cells accumulate methylthioadenosine (MTA) that inhibits PRMT5 methyltransferase activity [2,4]. In melanoma, reducing PRMT5 activity antagonizes melanoma growth in immunocompetent mice, and combination of PRMT5 inhibition with immune checkpoint therapy enhances therapeutic efficacy [5].

In conclusion, PRMT5 is essential for various cellular processes. Its study using gene knockout or conditional knockout models has revealed its significant roles in cancer, including promoting tumor metastasis, being a dependency in certain cancer metabolic states, and influencing antitumor immunity. These findings suggest that targeting PRMT5 could be a promising strategy for cancer therapy.