The CCN family is composed of six matrix proteins that function mainly in extracellular matrix (ECM) regulation.9–11 Among them, WISP-1, also called CCN4, has been studied the most extensively and is involved in fibrotic processes in a variety of organ systems.12,13 Previous work by our group showed that WISP-1 is highly expressed in hypertrophied LF tissue and is closely associated with LF fibrosis.14 However, little is known about the mechanism by which WISP-1 is activated and the downstream mechanism of WISP-1 in driving fibroblast activation in the context of LF fibrosis. The gene discussed is CCN4; the disease is fibrosis.