Ntsr2, belonging to the G protein-coupled receptor family, is a receptor for the neuropeptide neurotensin (NTS). It has been linked to various physiological and pathological processes. In the nervous system, it may play specific roles in analgesia, mental disorders, and is implicated in hematological cancers. It is also involved in the regulation of energy metabolism through its connection with adipose thermogenesis [2,1].

In adipose tissue, adenoviral-mediated knockdown or knockout of NTS (the ligand of Ntsr2) enhanced cold tolerance, suggesting that Ntsr2 and its associated ERK signaling pathway play a role in reducing cold tolerance by mediating the anti-thermogenic effect of NTS [1]. In chronic lymphocytic leukemia (CLL), Ntsr2, through recruitment of TRKB, induces survival pathways in leukemic B cells. A peptide targeting the binding domain of Ntsr2 and TRKB demonstrated cytotoxic effects both in vitro and ex vivo, highlighting its potential as a therapeutic target in CLL [3]. In mice, Ntsr2-deficient mice showed reduced freezing response in contextual fear-conditioning tests, suggesting its involvement in fear memory [4]. Also, Ntsr2-deficient mice had an altered jump latency in the hot plate test, indicating its role in thermal nociception [5].

In conclusion, Ntsr2 plays crucial roles in multiple biological processes such as adipose thermogenesis, fear memory, thermal nociception, and is involved in the survival of CLL cells. The study of Ntsr2 knockout mouse models has provided valuable insights into these functions, which may have implications for treating related diseases like obesity-related metabolic disorders and CLL.