SEC14L2, also known as tocopherol-associated protein (TAP), belongs to a family of lipid-binding proteins [6]. It is essential for regulating lipid-related processes. For instance, it plays a role in the phosphatidylinositol transfer, facilitating the conversion of phosphatidylinositol 4-phosphate (PtdIns4P) to phosphatidylinositol 3-phosphate (PtdIns3P) at the endosome fission site, which is crucial for endosomal cargo sorting and targeting [5]. It is also involved in cholesterol transport [2].

SEC14L2 has been found to be of great significance in multiple disease-related studies. In hepatitis C virus (HCV) research, SEC14L2 enables the replication of HCV isolates in cell culture, with different HCV genotypes reacting differently to its presence. All tested single-nucleotide polymorphisms (SNPs) of SEC14L2 supported HCV RNA replication in vitro, but one SNP was associated with decreased SEC14L2 expression and viral RNA [1,4]. In non-small cell lung cancer (NSCLC), SEC14L2 promotes cholesterol uptake by up-regulating SCARB1 expression, thereby promoting NSCLC development. Knockdown of SEC14L2 significantly reduces the proliferation and migration of NSCLC cells [2]. In oral squamous cell carcinoma (OSCC), high expression of SEC14L2 is associated with advanced tumor stages, grades, metastasis, and poor patient survival [3]. In castration-resistant prostate cancer (CRPC), low expression of SEC14L2 is associated with poorer disease-free survival, higher Gleason score, and promotes cell proliferation, migration, and invasion in CRPC cells [7]. In hepatocellular carcinoma (HCC), SEC14L2 exerts an anti-proliferative effect and strongly suppresses tumor growth in a mouse model [8]. In breast cancer, its expression is downregulated, raising the possibility of it being a tumor suppressor [9]. Also, in the Tibetan Chinese population, a SNP (rs1061660) in SEC14L2 is associated with an increased risk of pulmonary tuberculosis [10].

In conclusion, SEC14L2 is a key lipid-binding protein involved in various lipid-related biological processes. Its dysregulation is associated with multiple diseases, including viral infections, different types of cancers, and tuberculosis. Research on SEC14L2 using various models, though not specifically KO/CKO mouse models in the provided references, has enhanced our understanding of disease mechanisms, potentially paving the way for new therapeutic strategies.

References:

1. Costa, Rui, Todt, Daniel, Zapatero-Belinchón, Francisco, von Hahn, Thomas, Ciesek, Sandra. 2018. SEC14L2, a lipid-binding protein, regulates HCV replication in culture with inter- and intra-genotype variations. In Journal of hepatology, 70, 603-614. doi:10.1016/j.jhep.2018.11.012. https://pubmed.ncbi.nlm.nih.gov/30472319/

2. Zhou, Qianhui, Li, Dianwu, Liang, Yanchao, Long, Yunzhu, Liu, Yi. 2024. SEC14L2 regulates the transport of cholesterol in non-small cell lung cancer through SCARB1. In Lipids in health and disease, 23, 407. doi:10.1186/s12944-024-02401-9. https://pubmed.ncbi.nlm.nih.gov/39696431/

3. David, Jonah Justin, Kannan, Balachander, Pandi, Chandra, Vasagam, Jeevitha Manicka, Arumugam, Paramasivam. 2024. Increased SEC14L2 expression is associated with clinicopathological features and worse prognosis in oral squamous cell carcinoma. In Odontology, 112, 1326-1334. doi:10.1007/s10266-024-00929-x. https://pubmed.ncbi.nlm.nih.gov/38575815/

4. Saeed, Mohsan, Andreo, Ursula, Chung, Hyo-Young, Silva, Jose M, Rice, Charles M. 2015. SEC14L2 enables pan-genotype HCV replication in cell culture. In Nature, 524, 471-5. doi:10.1038/nature14899. https://pubmed.ncbi.nlm.nih.gov/26266980/

5. Gong, Bo, Guo, Yuting, Ding, Shihui, Li, Dong, Jia, Shunji. 2021. A Golgi-derived vesicle potentiates PtdIns4P to PtdIns3P conversion for endosome fission. In Nature cell biology, 23, 782-795. doi:10.1038/s41556-021-00704-y. https://pubmed.ncbi.nlm.nih.gov/34183801/

6. Qiu, Dandan, Kui, Xiuying, Wang, Wenguang, Lu, Caixia, Dai, Jiejie. 2022. Identification of SEC14 like lipid binding 2(SEC14L2) sequence and expression profiles in the Chinese tree shrew (Tupaia belangeri chinensis). In Molecular biology reports, 49, 7307-7314. doi:10.1007/s11033-022-07518-7. https://pubmed.ncbi.nlm.nih.gov/35767108/

7. Liu, Shiyun, Huang, Da, Huang, Jingyi, Xu, Danfeng, Na, Rong. 2021. Genome-wide Expression Analysis Identifies the Association between SEC14L2 and Castration-resistant Prostate Cancer Survival. In Journal of Cancer, 12, 2173-2180. doi:10.7150/jca.50299. https://pubmed.ncbi.nlm.nih.gov/33758595/

8. Li, Zhihui, Lou, Yi, Tian, Guoyan, Shi, Junping, Yang, Jin. 2019. Discovering master regulators in hepatocellular carcinoma: one novel MR, SEC14L2 inhibits cancer cells. In Aging, 11, 12375-12411. doi:10.18632/aging.102579. https://pubmed.ncbi.nlm.nih.gov/31851620/

9. Wang, Xi, Ni, Jing, Hsu, Chen-Long, Lee, Chia-Hwa, Yeh, Shuyuang. . Reduced expression of tocopherol-associated protein (TAP/Sec14L2) in human breast cancer. In Cancer investigation, 27, 971-7. doi:10.3109/07357900802392659. https://pubmed.ncbi.nlm.nih.gov/19909011/

10. Du, Baozhong, Hua, Demi, Droma, Ciren, Jin, Tianbo, Yang, Juan. 2017. Association between TAP2 and SEC14L2 polymorphisms and pulmonary tuberculosis risk in the Tibetan Chinese population. In International journal of clinical and experimental pathology, 10, 11188-11194. doi:. https://pubmed.ncbi.nlm.nih.gov/31966469/