THBS4 (thrombospondin-4) is an adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions through integrin binding and extracellular matrix modulation. Primary functions include regulating cellular proliferation, migration, and inflammatory responses across multiple tissues 1. Mechanistically, THBS4 operates through several pathways. In keratinocytes, it activates signaling cascades controlling proliferation, migration, and inflammation-related genes 1. In pulmonary arterial hypertension, THBS4 promotes smooth muscle cell phenotype transformation and proliferation via PI3K/AKT pathway activation 2. In cardiac tissue, THBS4 regulates endoplasmic reticulum stress responses through interaction with transcriptional regulators, enabling adaptive remodeling under pressure overload 3. In cancer cells, THBS4 promotes proliferation and metastasis by interacting with integrin-β1 and activating FAK/PI3K/AKT signaling 4. Disease relevance spans multiple pathologies: THBS4 predicts poor prognosis in gastric cancer via KLF9-dependent mechanisms 5, accumulates in Alzheimer disease β-amyloid plaques with sex-specific effects on gray matter volumes 6, and increases in Duchenne muscular dystrophy muscle lesions during fibrosis and calcification 7. Clinically, elevated circulating THBS4 distinguishes irreversible from reversible pulmonary arterial hypertension in congenital heart disease, offering diagnostic and therapeutic potential 2. THBS4 shows promise as a wound healing therapeutic target 1 and influences systemic proteome in metformin-treated diabetes patients 8.