SPINT1 is a membrane-anchored serine protease inhibitor that regulates pericellular proteolysis through inhibition of multiple serine proteases, including HGFAC, matriptase (ST14), and TMPRSS13. It functions in epithelial development and extracellular matrix organization, with expression documented in pancreatic epithelium, choroid plexus epithelial cells, and multiple other tissues. In pancreatic β cells, SPINT1 modulates glucose homeostasis and insulin production via HEPSIN/MAFA signaling, and its expression is elevated in prediabetic individuals 1. SPINT1 has clinical relevance across multiple disease contexts. Low circulating SPINT1 concentrations at 36 weeks' gestation associate with placental insufficiency and fetal growth restriction, with a 2–5 fold increased risk of delivering neonates with low birthweight in the highest-risk tier 2. In breast carcinoma, elevated SPINT1 expression correlates with poorer prognosis and is upregulated particularly in HER2-positive and node-positive patients 3. Increased SPINT1 expression also associates with enhanced drug sensitivity to STAT3/STAT5 degraders in T-prolymphocytic leukemia 4. Changes in SPINT1 gene promoter methylation have been identified as a potential diagnostic biomarker for Alzheimer disease and amnestic mild cognitive impairment, with 63.8% sensitivity and 83.3% specificity 5.