Two separate studies outlined new protein-level mechanisms for chronic hepatitis B control, both linking innate antiviral effectors to HBV biology. One report described IFI35 degrading HNF4α to block HBV cccDNA transcription, while another mapped TRIM22’s pathway to suppress viral replication by tagging LDHA for destruction. Taken together, the findings reinforce a shift toward therapeutic strategies that modulate host transcriptional control and metabolism rather than only targeting viral components, offering additional starting points for combination designs in HBV.