Esr2, also known as estrogen receptor β (ERβ), is one of the main nuclear receptors for estrogens. Estrogens, through binding to Esr2, regulate various biological processes in both male and female reproductive and non-reproductive organs [3]. It is also involved in pathways related to glucose metabolism [4], and may play a role in the estrogen signaling pathway [5]. Genetic models, such as knockout (KO) mouse models, are valuable for studying its functions.

In terms of disease-related findings, the polymorphism of Esr2 rs1256049 is associated with a higher risk of prostate cancer (PCa) in the Caucasian population and a lower risk in the Asian population, while rs4986938 was not associated with PCa risk [1]. In knee osteoarthritis, Lipoxin A4 can inhibit ferroptosis in synovial fibroblast-like synoviocytes by activating the ESR2/LPAR3/Nrf2 axis, alleviating pain and pathological progression [2]. In breast cancer, the rs1256030 variant of the ESR2 gene and haplotype GAT were associated with susceptibility as risk factors in a Mexican population sample [6].

In conclusion, Esr2 is crucial in estrogen-mediated regulation of multiple biological processes. Studies using gene-knockout models have revealed its role in various disease conditions, including prostate cancer, knee osteoarthritis, and breast cancer. These findings contribute to a better understanding of the molecular mechanisms underlying these diseases and may provide potential targets for treatment.