S100A11 is a calcium-binding protein that functions as a multifunctional regulator in cellular signaling and metabolism. Structurally, it belongs to the S100 family characterized by EF-hand motifs and typically forms dimers 1. Beyond its reported role in keratinocyte differentiation, S100A11 plays significant roles in disease pathogenesis across multiple organ systems. In metabolic disease, S100A11 promotes hepatic steatosis through two distinct mechanisms: it activates FOXO1-mediated autophagy and lipogenesis via interaction with HDAC6 2, and separately activates RAGE-mediated AKT-mTOR signaling to induce lipid synthesis 3. Elevated S100A11 expression correlates with nonalcoholic fatty liver disease severity in both patients and animal models. In cancer, S100A11 emerges as a key mediator of tumor progression. In hepatocellular carcinoma, S100A11 promotes cancer stemness and maintains stem cell markers, with S100A11-expressing tumor cells displaying enhanced crosstalk with tumor-associated macrophages 4. In colorectal cancer, S100A11 knockdown inhibits proliferation and invasion by promoting cell senescence, with USP14-mediated deubiquitination regulating S100A11 stability 5. In inflammatory conditions, S100A11 is significantly upregulated in ulcerative colitis macrophages and serves as a potential biomarker 6. In sepsis, elevated S100A11 levels associate with improved 28-day survival rates 7. S100A11 also functions as an oncogene in hepatocellular carcinoma, suppressed by H3K9me3 modification 8.