ITGBL1 (integrin subunit beta like 1) is an extracellular matrix protein that functions as a critical regulator of cell adhesion, migration, and fibrogenic processes across multiple pathological contexts. Primary Function: ITGBL1 mediates integrin-dependent signaling pathways essential for cell-matrix and cell-cell interactions 1. The protein localizes to focal adhesions and the plasma membrane, where it facilitates integrin complex assembly and downstream signaling events. Mechanistic Actions: ITGBL1 operates through multiple signaling axes depending on cellular context. In cancer cells, it activates AKT phosphorylation to promote proliferation and invasion 12. In fibrotic contexts, ITGBL1 expression is regulated by the SMYD3/H3K4me3 epigenetic pathway and promotes myofibroblast differentiation via integrin β1/ILK signaling 3. ITGBL1 is also packaged into extracellular vesicles released by primary tumors to activate stromal fibroblasts through TNFAIP3-mediated NF-κB signaling 4, and is secreted by fibroblasts to promote skin development through TGFβ1-SMAD2/3 activation 5. Disease Relevance: ITGBL1 promotes gastric cancer metastasis and anoikis resistance via the AKT/FBLN2 axis 2, facilitates pre-metastatic niche formation in colorectal cancer 4, mediates castration-resistant prostate cancer progression 6, drives HBV-induced liver fibrosis via RUNX2-regulated expression 7, and contributes to pathological wound scarring 8. Clinical Significance: High ITGBL1 expression correlates with poor prognosis in gastric cancer patients 2. Targeting ITGBL1 or its regulatory pathways represents a therapeutic strategy for metastatic cancer, liver fibrosis, and excessive scarring 73.