LCTL, also known as KLPH, belongs to the Klotho family of proteins. It coordinates the interaction between different FGF ligands and the FGF receptor, and may be involved in multiple biological processes. In lens development, it is essential for the expression of Clic5 and normal lens suture formation [2].

In gliomas, LCTL is highly expressed, and its expression is regulated by DNA methylation at the promoter. Mechanistically, it might play an immunosuppressive role by recruiting immunosuppressive cells and regulating multiple aspects like tumor-associated macrophages polarization, T cell exhaustion, and epithelial-mesenchymal transition through FGF signaling. High LCTL expression is associated with high tumor aggressiveness and poor outcomes for glioma patients, establishing it as a prognostic biomarker and a potential epigenetic and immunotherapeutic target [1]. In the context of COVID-19, higher levels of LCTL in blood were associated with a decreased risk of hospitalization [3]. For clear cell renal cell carcinoma, LCTL is one of the four genes used to construct a sarcomatoid-associated gene risk index (SAGRI), which can predict patient prognosis, and the SAGRI-HIGH subgroup may benefit more from immunotherapy [4].

In conclusion, LCTL plays diverse and significant roles in various biological processes and disease conditions. Its functions in glioma immune evasion, lens development, COVID-19 risk, and renal cell carcinoma prognosis have been revealed through research. The study of LCTL provides insights into disease mechanisms and potential therapeutic targets in these areas.

References:

1. Su, Jun, Ma, Qianquan, Long, Wenyong, Li, Haoyu, Liu, Qing. 2019. LCTL Is a Prognostic Biomarker and Correlates With Stromal and Immune Infiltration in Gliomas. In Frontiers in oncology, 9, 1083. doi:10.3389/fonc.2019.01083. https://pubmed.ncbi.nlm.nih.gov/31681612/

2. Fan, Jianguo, Lerner, Joshua, Wyatt, M Keith, Dong, Lijin, Wistow, Graeme. 2018. The klotho-related protein KLPH (lctl) has preferred expression in lens and is essential for expression of clic5 and normal lens suture formation. In Experimental eye research, 169, 111-121. doi:10.1016/j.exer.2018.02.001. https://pubmed.ncbi.nlm.nih.gov/29425878/

3. Palmos, Alish B, Millischer, Vincent, Menon, David K, Hübel, Christopher, Breen, Gerome. 2022. Proteome-wide Mendelian randomization identifies causal links between blood proteins and severe COVID-19. In PLoS genetics, 18, e1010042. doi:10.1371/journal.pgen.1010042. https://pubmed.ncbi.nlm.nih.gov/35239653/

4. Zuo, You, Fu, Shuai, Zhao, Zhongwei, Xu, Zhonghua, Yu, Nengwang. 2022. Sarcomatoid-associated gene risk index for clear cell renal cell carcinoma. In Frontiers in genetics, 13, 985641. doi:10.3389/fgene.2022.985641. https://pubmed.ncbi.nlm.nih.gov/36159988/