ECM1 (extracellular matrix protein 1) is a multifunctional extracellular matrix protein with primary roles in tissue homeostasis and inflammatory regulation. Mechanistically, ECM1 stabilizes latent transforming growth factor-β1 (TGF-β1) through interactions with αv integrins and inhibits its activation by binding thrombospondins and ADAMTS proteases via their KRFK/KTFR motifs 12. ECM1 also suppresses matrix metalloproteinase-2/9 proteolytic activity 2 and regulates macrophage M1 polarization through granulocyte-macrophage colony-stimulating factor/STAT5 signaling 3. Clinically, ECM1 deficiency causes spontaneous hepatic fibrosis and requires early therapeutic intervention 1. ECM1 expression inversely correlates with liver fibrosis severity in chr1 liver disease patients 12. The protein protects against metabolic dysfunction-associated steatotic liver disease by maintaining iron homeostasis via PCBP1 interaction 4. ECM1 also suppresses anti-androgen resistance in bone metastatic prostate cancer through ENO1 receptor signaling 5, and its downregulation alleviates inflammatory kidney disease 6. Genetically, ECM1 mutations cause lipoid proteinosis, a rare autosomal recessive disorder featuring skin infiltration, neuropsychiatric abnormalities, and amygdala calcifications 7. Mendelian randomization analysis suggests ECM1 elevation may exacerbate aging processes 8.