Fibronectin glomerulopathy is likely a rare condition, although its prevalence is unknown. At least 45 cases have been described in the scientific literature.

Fibronectin glomerulopathy can be caused by mutations in the FN1 gene. The FN1 gene provides instructions for making the fibronectin-1 protein. Fibronectin-1 is involved in the continual formation of the extracellular matrix, which is an intricate lattice of proteins and other molecules that forms in the spaces between cells. During extracellular matrix formation, fibronectin-1 helps individual cells expand (spread) and move (migrate) to cover more space, and it also influences cell shape and maturation (differentiation).

FN1 gene mutations lead to production of an abnormal fibronectin-1 protein that gets deposited in the glomeruli of the kidneys, probably as the body attempts to filter it out as waste. Even though there is an abundance of fibronectin-1 in the glomeruli, the extracellular matrix that supports the blood vessels is weak because the altered fibronectin-1 cannot assist in the matrix's continual formation. Without a strong cellular support network, the glomeruli are less able to filter waste. As a result, products that normally are retained by the body, such as protein and blood, get released in the urine, and acids are not properly filtered from the blood. Over time, the kidneys' ability to filter waste decreases until the kidneys can no longer function, resulting in end-stage renal disease.

It is estimated that mutations in the FN1 gene are responsible for 40 percent of cases of fibronectin glomerulopathy. The cause of the remaining cases of this condition is unknown.