Aplnr, also known as Apelin receptor or APJ, is a seven-transmembrane G protein-coupled receptor. It plays a crucial role in multiple physiological and pathological processes. The Apelin/APLNR system is involved in regulating autophagy, apoptosis, pyroptosis, and participates in immune response and regulation through pathways like PI3K-Akt and ERK-MAPK. It is also important in cardiovascular homeostasis, hematopoiesis, and cell migration [1,2,5,6]. Genetic models, such as gene knockout mouse models, are valuable for studying Aplnr's functions.

Aplnr knockout mice display sex-specific changes in conditioned fear, with male knockout mice showing enhanced context-and cue-dependent fear responses, indicating its role in the central nervous system [3]. In the hematopoietic system, deletion of Aplnr from mouse embryonic stem cells impairs the production of hematopoietic stem and progenitor cells, suggesting that APLNR signaling is required for their generation [5]. Knockdown of Aplnr in osteosarcoma cells inhibits cell proliferation and invasion in vitro, and Aplnr promotes osteosarcoma progression and metastasis in mice, indicating its role in this malignancy [4].

In conclusion, Aplnr is essential in various biological processes, including the central nervous system function, hematopoiesis, and tumor development. Gene knockout mouse models have significantly contributed to understanding Aplnr's role in these areas, providing insights into its functions and potential as a therapeutic target for diseases such as certain cancers and neurological disorders.