EFEMP1, also known as epidermal growth factor-containing fibulin-like extracellular matrix protein 1, is involved in multiple biological processes. It is likely to participate in extracellular matrix-related functions and may be associated with pathways influencing cell-matrix interactions, angiogenesis, and tissue homeostasis. Its importance spans across various biological systems and is crucial for normal physiological functions [1-10].

EFEMP1 has been linked to numerous disease conditions. In bladder cancer, the METTL1-m7G-EGFR/EFEMP1 axis promotes cancer development, with METTL1 regulating the translation of EFEMP1 through tRNA modification [1]. Haploinsufficiency of EFEMP1 due to nonsense-mediated decay can cause a Marfan-like hereditary connective tissue disorder, presenting symptoms such as severe kyphoscoliosis and joint hypermobility [2]. Rare EFEMP1 coding variants can lead to familial juvenile-onset open-angle glaucoma through protein aggregation and retention mechanisms [3,9]. In age-related macular degeneration, EFEMP1 overexpression contributes to neovascularization, making it a potential biomarker for choroidal neovascularization in AMD [4]. In zebrafish, efemp1 regulates light-dependent ocular growth, and in myopia patients, EFEMP1 may be involved in regulating choroidal thickness [5,6]. In osteosarcoma, serum EFEMP1 levels can be used to distinguish patients from healthy controls and as an indicator for lung metastasis [7]. In direct inguinal hernia, EFEMP1 is downregulated and regulates elastin homeostasis and fibroblast mobility [8]. Also, EFEMP1 has been implicated as a determinant of neurodegeneration in proteomic analyses [10].

In conclusion, EFEMP1 is essential for maintaining normal physiological functions in multiple biological systems. Model-based research, especially in understanding its role in diseases like cancer, connective tissue disorders, glaucoma, age-related macular degeneration, myopia, osteosarcoma, inguinal hernia, and neurodegeneration, has provided valuable insights. These studies on EFEMP1 contribute to a better understanding of disease mechanisms and may potentially lead to the development of new diagnostic and therapeutic strategies.

References:

1. Ying, Xiaoling, Liu, Bixia, Yuan, Zusen, Luo, Junhang, Ji, Weidong. . METTL1-m7 G-EGFR/EFEMP1 axis promotes the bladder cancer development. In Clinical and translational medicine, 11, e675. doi:10.1002/ctm2.675. https://pubmed.ncbi.nlm.nih.gov/34936728/

2. Forghani, Irman, Lang, Steven H, Rodier, Matthew J, Bademci, Guney, Tekin, Mustafa. 2024. EFEMP1 haploinsufficiency causes a Marfan-like hereditary connective tissue disorder. In American journal of medical genetics. Part A, 194, e63556. doi:10.1002/ajmg.a.63556. https://pubmed.ncbi.nlm.nih.gov/38348595/

3. Collantes, Edward Ryan A, Delfin, Manuel S, Fan, Baojian, Rong, Shisong, Wiggs, Janey L. 2021. EFEMP1 rare variants cause familial juvenile-onset open-angle glaucoma. In Human mutation, 43, 240-252. doi:10.1002/humu.24320. https://pubmed.ncbi.nlm.nih.gov/34923728/

4. Cheng, Lu, Chen, Chong, Guo, Wenke, Yu, Fudong, Xu, Xun. 2021. EFEMP1 Overexpression Contributes to Neovascularization in Age-Related Macular Degeneration. In Frontiers in pharmacology, 11, 547436. doi:10.3389/fphar.2020.547436. https://pubmed.ncbi.nlm.nih.gov/33584252/

5. Xie, Jiaheng, Bui, Bang V, Goodbourn, Patrick T, Jusuf, Patricia R. 2024. EFEMP1 contributes to light-dependent ocular growth in zebrafish. In Biology open, 13, . doi:10.1242/bio.061741. https://pubmed.ncbi.nlm.nih.gov/39607017/

6. Shi, Wen-Qing, Wan, Ting, Li, Bing, Li, Tao, Zhou, Xiao-Dong. 2023. EFEMP1 is a potential biomarker of choroid thickness change in myopia. In Frontiers in neuroscience, 17, 1144421. doi:10.3389/fnins.2023.1144421. https://pubmed.ncbi.nlm.nih.gov/36891459/

7. Wang, Zhuo, Kang, Jihui, Lian, Jiayan, Ma, Huisi, Lin, Zhongwei. 2020. EFEMP1 as a Potential Biomarker for Diagnosis and Prognosis of Osteosarcoma. In BioMed research international, 2020, 5264265. doi:10.1155/2020/5264265. https://pubmed.ncbi.nlm.nih.gov/32280689/

8. Peng, Xiaohui, Guo, Zhongwu, Zhang, Yinlong, Sun, Baichen, Zhang, Qi. 2020. EFEMP1 in Direct Inguinal Hernia: correlation with TIMP3 and Regulation Toward Elastin Homoeostasis as Well as Fibroblast Mobility. In Journal of investigative surgery : the official journal of the Academy of Surgical Research, 35, 203-211. doi:10.1080/08941939.2020.1811812. https://pubmed.ncbi.nlm.nih.gov/33131351/

9. Collantes, Edward Ryan A, Delfin, Manuel S, Fan, Baojian, Rong, Shisong, Wiggs, Janey L. 2022. EFEMP1 rare variants cause familial juvenile-onset open-angle glaucoma. In Human mutation, 43, 1343. doi:10.1002/humu.24395. https://pubmed.ncbi.nlm.nih.gov/35490425/

10. Duggan, Michael R, Yang, Zhijian, Cui, Yuhan, Davatzikos, Christos, Walker, Keenan A. 2024. Proteomic analyses reveal plasma EFEMP1 and CXCL12 as biomarkers and determinants of neurodegeneration. In Alzheimer's & dementia : the journal of the Alzheimer's Association, 20, 6486-6505. doi:10.1002/alz.14142. https://pubmed.ncbi.nlm.nih.gov/39129354/