During embryonic development, CYR61 is critical for cardiac septal morphogenesis, blood vessel formation in placenta, and vascular integrity.

[9][10][11] The CCN acronym is derived from the first three members of the family identified, namely CYR61 (CCN1), CTGF (connective tissue growth factor, or CCN2), and NOV (nephroblastoma overexpressed, or CCN3).

The 5th exon also contains the 3’-UTR sequences, which has 5 copies of AU-rich elements that confers a short mRNA half life, and a mir-155 target site.

Full-length CYR61 protein contains 381 amino acids with an N-terminal secretory signal peptide followed by four structurally distinct domains.

[30] CYR61 has potent angiogenic activity upon endothelial cells and induces neovascularization, first demonstrated in a corneal micropocket implant assay[31] and subsequently confirmed in a rabbit ischemic hindlimb model.

[34][35][36] Cyr61 is a strong inducer of reactive oxygen species accumulation in fibroblastic cells, and this activity underlies many CYR61-induced apoptosis and senescence.

[37][38] Cyr61 knockout mice are embryonic lethal due to defects in cardiac septal morphogenesis, deficient blood vessel formation in placenta, and compromised vascular integrity.

[44] In addition to skin wound healing, CYR61 expression is elevated in remodeling cardiomyocytes after myocardial infarction,[45] in vascular injury,[20] and in the long bones during fracture repair.

[53] CYR61 supports the patrolling behavior of murine resident Ly6Clow monocytes along the endothelial in the steady state and is required for their accumulation under viral-mimicking vascular inflammation.

[56] CYR61 is overexpressed in vascular smooth muscle cells of atherosclerotic lesions and in the neointima of restenosis after balloon angioplasty, both in rodent models and in humans.

[20][22][57][58] Suppression of CYR61 expression results in reduced neointimal hyperplasia after balloon angioplasty, an effect that is reversed by delivery of CYR61 via gene transfer[59][60] In a mouse model of oxygen-induced retinopathy, expression of CYR61 in the vitreous humor produced significant beneficial effects in repairing damaged vasculature.

[62] CYR61 is a powerful angiogenic inducer in vivo,[31][32] and it can also promote cancer cell proliferation, invasion, survival, epithelial–mesenchymal transition, and metastasis.