Ninj2, also known as nerve injury-induced protein 2, is involved in multiple biological processes. It plays roles in regulating cell-cell signaling pathways, such as laminin-integrin signaling, insulin signaling, and IGF1R-related signaling. It is of great biological importance as it impacts myelination in the nervous system, adipogenesis, insulin resistance, and liver fibrosis, among others. Genetic models, especially gene knockout (KO) mouse models, have been crucial in studying Ninj2's functions [1-3, 4].

In SC-specific Ninj2 knockout (Dhhcre/+;Ninj2fl/fl) mice, Ninj2 was found to negatively regulate Schwann cells (SC) development. The Ninj2-deficient mice showed precocious myelination and accelerated remyelination after sciatic nerve injury. Mechanistically, Ninj2 interacted with ITGB1 on the SC membrane, inhibiting laminin-integrin signaling, and its removal activated this signaling to improve myelination [1]. NINJ2 knockout mice also showed impaired adipogenesis, increased insulin resistance, and abnormal glucose homeostasis. NINJ2 directly interacted with insulin receptor/insulin-like growth factor 1 receptor (INSR/IGF1R), and its knockdown blocked insulin-induced mitotic clonal expansion during preadipocyte differentiation [2]. In liver fibrosis studies, global Ninj2 knockout reversed the fibrotic phenotype, while hepatocyte-specific Ninj2 overexpression exacerbated it. Ninj2 interacted with IGF1R in hepatocytes and increased the secretion of PDGF-BB through the IGF1R-PI3K-AKT-EGR1 cascade to activate hepatic stellate cells [3]. Mice with oligodendrocyte-specific deletion of Ninj2 exhibited depressive-like behaviors due to inhibited oligodendrocyte development and myelination [4].

In conclusion, Ninj2 is a multi-functional gene involved in myelination, adipogenesis, insulin resistance, and liver fibrosis. KO mouse models have been instrumental in revealing its role in these biological processes and associated disease conditions such as nerve injury-related myelination disorders, metabolic diseases related to insulin resistance, and liver fibrosis. This research provides insights into potential therapeutic targets for these diseases [1-4].