Fig. 9: Graphical abstract: LAPTM5 exacerbates STING-mediated inflammation induced by LL-37 through stabilizing STING in rosacea.

In rosacea, elevated LL-37 induces nuclear damage in lesional skin, leading to the release of nuclear DNA fragments into the cytoplasm and even the extracellular environment. These DNA fragments activate macrophage cGAS-STING signaling pathway and trigger the production of type I interferons and pro-inflammatory cytokines. LAPTM5 is upregulated by LL-37 in macrophages and interacts with STING, inhibiting its K48- and K63-linked polyubiquitination. By preventing both proteasomal and lysosomal degradation, LAPTM5 maintains STING protein stability under both resting and activated conditions, thereby enhancing STING signaling and exacerbating inflammation in rosacea. Illustration elements (human face and skin) were obtained from Figdraw 2.0.