FIGURE 2.

Functional regulation of UFMylation in innate immunity. The UFM1 system regulates antiviral responses and inflammatory pathways. UFL1 interacts with STING to prevent its ubiquitination and proteasomal degradation upon HSV‐1 infection. ⁹ Increased interaction between 14‐3‐3ε and UFL1 leads to UFMylation and subsequent binding to K63‐ubiquitinated RIG‐Ι, enhancing downstream IFN signalling during SenV infection. ⁷ The EBV‐encoded BILF1 mediates MAVS UFMylation, targeting it for lysosomal degradation and potentially disrupting NLRP3 inflammasome activation and IRF3 responses. ⁸ The UFM1 system suppress the proinflammatory capacity of IFN‐γ or LPS‐mediated macrophage activation, ¹³ and inhibits NF‐κB activation with unclear mechanisms. ⁷⁷ , ⁷⁹ During AS development, UFM1 plays a role in reducing foamy cells formation by activating LXRα and supressing the expression of pro‐inflammatory cytokines produced by LPS‐activated endothelial cells. ¹⁸ , ⁷⁷ In mucosal barrier, UFBP1 deletion results in ER‐stress‐induced apoptosis in Goblet and Paneth cells, alterations in the faecal microbiota and increased susceptibility to inflammatory colitis. ¹⁶