Notably, RNF5 demonstrates a pronounced antiviral effect in both in vitro and in vivo settings (Figs 2 and 6), with the RNF5 activator Analog-1 proving to be effective in inhibiting FMDV replication in infection models utilizing cultured cells and mice, thereby positioning it as a potential therapeutic agent against FMDV infections (Fig 7). Here, RNF5 is linked to infection.