Fibronectin type III domain-containing protein 4 (FNDC4)

Fibronectin type III domain-containing protein 4 (FNDC4) is a member of the FNDC family of proteins characterized by containing one or more fibronectin type III domains. FNDC4 is an extracellular matrix-associated protein that can be cleaved and released as soluble FNDC4 (sFNDC4), which acts as a signaling molecule. It regulates inflammation, metabolism, and cell differentiation, particularly in immune cells (macrophages), adipocytes, osteoclasts, and muscle cells. FNDC4 is upregulated during inflammatory states and is associated with protective effects, such as promoting an anti-inflammatory macrophage phenotype, improving insulin sensitivity, and inhibiting osteoclast differentiation. Changes in FNDC4 concentration are linked to the prognosis of cancer, metabolic, bone, and cardiovascular diseases, making it both a putative biomarker and therapeutic target for these indications. Research into FNDC4 function is ongoing, with promising but not yet clinically translated findings.

Other names

Fibronectin type III domain containing 4Soluble FNDC4FRCP1UNQ6389/PRO21134sFNDC4FLJ22362fibronectin type III repeat-containing protein 1FNDC4

Recombinant FNDC4 supplementation: reduces inflammation by signaling to macrophages, suppressing phagocytosis, cytokine secretion, and activating signal pathways that promote quiescent, anti-inflammatory macrophages. Cleaved soluble FNDC4 (sFNDC4) acts as an extracellular factor, modulating cell signaling linked to inflammation, lipid metabolism, and osteoclast differentiation.