Cd24a, encoding the mucin-like GPI-linked membrane protein CD24, is involved in multiple biological functions. It plays a role in regulating the immune response, as it can associate with proteins like high mobility group box 1, heat shock protein 70, and 90, negatively regulating their stimulatory activity and inhibiting NF-κB activation through its association with Siglec-10 in humans or Siglec-G in mice [2]. It is also important in cell-type discrimination, such as distinguishing Langerhans cells from dermal dendritic cells in murine skin and lymph nodes based on its expression levels [3].

In the context of diseases, in acute kidney injury (AKI) murine models, AKI induced proximal tubule dedifferentiation with a pronounced nephrogenic signature represented by Sox4 and Cd24a [1]. In multiple sclerosis, a single-nucleotide polymorphism in the CD24 gene results in an amino-acid replacement, with the CD24v/v genotype increasing the relative risk of MS and accelerating disease progression compared to CD24a/v and CD24a/a genotypes [4]. In hepatocellular carcinoma, CD24A (an isoform of CD24) promotes cell proliferation, migration, and invasion, and is downregulated by EGR1 [5]. In the lens, Cd24a-null mice develop normal lenses that become opaque with abnormal fiber cell structure and refractive defects by 1 year of age, indicating its role in maintaining lens transparency [6].

In conclusion, Cd24a is essential in immune regulation, cell-type discrimination, and maintaining tissue homeostasis. Studies using gene-knockout mouse models, especially in diseases like AKI, multiple sclerosis, hepatocellular carcinoma, and lens-related pathologies, have revealed its crucial functions in disease development and progression, providing potential targets for therapeutic intervention.

References:

1. Rudman-Melnick, Valeria, Adam, Mike, Potter, Andrew, Devarajan, Prasad, Potter, S Steven. 2020. Single-Cell Profiling of AKI in a Murine Model Reveals Novel Transcriptional Signatures, Profibrotic Phenotype, and Epithelial-to-Stromal Crosstalk. In Journal of the American Society of Nephrology : JASN, 31, 2793-2814. doi:10.1681/ASN.2020010052. https://pubmed.ncbi.nlm.nih.gov/33115917/

2. Chen, Guo-Yun, Tang, Jie, Zheng, Pan, Liu, Yang. 2009. CD24 and Siglec-10 selectively repress tissue damage-induced immune responses. In Science (New York, N.Y.), 323, 1722-5. doi:10.1126/science.1168988. https://pubmed.ncbi.nlm.nih.gov/19264983/

3. Stutte, Susanne, Jux, Bettina, Esser, Charlotte, Förster, Irmgard. 2008. CD24a expression levels discriminate Langerhans cells from dermal dendritic cells in murine skin and lymph nodes. In The Journal of investigative dermatology, 128, 1470-5. doi:10.1038/sj.jid.5701228. https://pubmed.ncbi.nlm.nih.gov/18185529/

4. Zhou, Qunmin, Rammohan, Kottil, Lin, Shili, Zheng, Pan, Liu, Yang. 2003. CD24 is a genetic modifier for risk and progression of multiple sclerosis. In Proceedings of the National Academy of Sciences of the United States of America, 100, 15041-6. doi:. https://pubmed.ncbi.nlm.nih.gov/14657362/

5. Li, Liangyu, Chen, Jing, Ge, Chao, Li, Jinjun, Li, Hong. 2019. CD24 isoform a promotes cell proliferation, migration and invasion and is downregulated by EGR1 in hepatocellular carcinoma. In OncoTargets and therapy, 12, 1705-1716. doi:10.2147/OTT.S196506. https://pubmed.ncbi.nlm.nih.gov/30881025/

6. Shihan, Mahbubul H, Balasubramanian, Ramachandran, Wang, Yan, Nie, Xingju, Duncan, Melinda K. 2025. CD24 is required for sustained transparency of the adult lens. In Experimental eye research, 255, 110347. doi:10.1016/j.exer.2025.110347. https://pubmed.ncbi.nlm.nih.gov/40112946/