NRBP1, or nuclear receptor-binding protein 1, is an adaptor protein with multiple domains and has been implicated in various biological functions and pathways. It is evolutionarily highly conserved. In the nervous system, it may be involved in synaptic maintenance and neurodegeneration-related processes. In addition, it has connections with multiple signaling pathways such as the PI3K/Akt, Wnt/β-catenin, and WNK pathways, influencing cell proliferation, migration, apoptosis, ion transport, and other physiological processes [2,3,5]. Genetic models, especially knockout (KO) mouse models, can be valuable for studying its functions.

In a mouse model of chronic social defeat stress, (R)-ketamine increased NRBP1 expression in microglia of the medial prefrontal cortex, and this was part of an ERK-NRBP1-CREB-BDNF signaling pathway underlying the antidepressant-like effects of (R)-ketamine [1]. In glioblastoma (GBM) cells, NRBP1 knockout suppressed cell proliferation, invasion, and migration both in vitro and in vivo, indicating its role in promoting GBM malignant phenotypes by activating the PI3K/Akt pathway [2]. In a mouse model of bladder cancer, NRBP1 knockdown significantly inhibited cell proliferation and induced apoptosis in vitro and suppressed tumor growth in a xenograft mouse model, suggesting its importance in bladder cancer development [4].

In conclusion, NRBP1 is involved in multiple biological functions. Studies using KO mouse models have revealed its significance in diseases like depression, glioblastoma, and bladder cancer. These findings contribute to understanding the mechanisms of these diseases and may potentially lead to new therapeutic targets related to NRBP1.