Tango Therapeutics presented preclinical data on TNG‑456, a selective MTA‑cooperative PRMT5 inhibitor that produced strong antitumor activity in glioma models and tumors that metastasize to the brain. The compound’s mechanism exploits methyltransferase vulnerabilities in tumor cells. Separately, new research linked PRMT5 overexpression to worsened cardiac hypertrophy and heart failure in pressure‑overload models, highlighting potential safety considerations for systemic PRMT5 inhibition. The twin reports underscore both therapeutic potential and biomarker‑guided risk assessment needs for PRMT5‑directed programs.