PRELP, the proline-and arginine-rich end leucine-rich repeat protein, is a small leucine-rich proteoglycan (SLRP) that binds different types of collagen [3]. It plays a role in various biological processes such as cell-cell adhesion, and is involved in regulating extracellular matrix (ECM)-related functions. It has been associated with multiple signaling pathways including the wnt/β-catenin, NF-κB, and integrin-related pathways, and is of great importance in understanding fibrosis, cancer, and neurovascular integrity [1,2,4-8]. Genetic models, especially knockout (KO) mouse models, have been crucial in studying its functions.

In fibrosis, Prelp-knockdown in cardiac and liver myofibroblasts reduced collagen expression, indicating its role in promoting collagen production in fibrotic hearts and livers [1]. In retinoblastoma, mRNA expression profiling of PRELP-/-mouse retina and PRELP-treated RB cells showed that loss of PRELP reduces cell-cell adhesion and facilitates EMT, suggesting its potential as a treatment strategy [2]. In the context of the blood-brain barrier, Prelp-/-mice presented with neuroinflammation, reduced neurovasculature integrity, and suppressed adhesion junction protein expression, highlighting PRELP's role in maintaining endothelial cell-cell integrity [4].

In conclusion, PRELP has diverse essential biological functions, including regulating collagen production in fibrosis, cell-cell adhesion in cancer, and neurovascular integrity. The use of Prelp KO mouse models has significantly contributed to understanding its role in diseases such as fibrosis, retinoblastoma, and neurovascular-related disorders, providing potential therapeutic targets for these conditions.