Tnfsf11, also known as RANKL (Receptor Activator of NF-κB Ligand), is a key cytokine in the RANKL/RANK/OPG pathway. It is crucial for osteoclast differentiation and activation, playing a significant role in bone metabolism [2]. Dysregulation of this pathway can lead to various bone-related diseases. Additionally, it is involved in immune-related processes during pregnancy and in the development of certain cancers [3,4].

In lung adenocarcinoma, overexpression of Tnfsf11 reduces GPX4 levels and increases sensitivity to ferroptosis inducers. Gene knockdown or overexpression experiments demonstrated that Tnfsf11 negatively regulates GPX4, providing potential therapeutic targets for this malignancy [1].

In preeclampsia, polymorphisms in the Tnfsf11 gene (rs2200287 and rs2148072) were associated with the disease, suggesting its role in the immune-related aspects of pregnancy [3].

In membranous nephropathy, the miR-149-5p/TNFSF11 pathway was found to be involved in angiotensin II-induced podocyte apoptosis, where TNFSF11 upregulation increased apoptosis under angiotensin II stimulation [5].

In conclusion, Tnfsf11 is essential for osteoclast-mediated bone resorption and has implications in multiple disease areas such as lung adenocarcinoma, preeclampsia, and membranous nephropathy. Functional studies, including gene knockdown experiments, have revealed its regulatory role in key cellular processes within these diseases, highlighting its potential as a therapeutic target.