Mylip, also known as Idol (inducible degrader of the LDL receptor), is an E3 ubiquitin ligase. It plays a crucial role in cholesterol metabolism by enhancing the ubiquitination of the LDL receptor, thus regulating plasma LDL levels. The LXR-Idol-LDLR axis is a complementary pathway to sterol response element-binding proteins for sterol regulation of cholesterol uptake [1,2].

In prostate cancer cells, MYLIP ubiquitinates the androgen receptor (AR), leading to its degradation through the ubiquitin-proteasome pathway. CNPY2 can inhibit this process by decreasing the ubiquitination activity of MYLIP, promoting the growth of prostate cancer cells [3]. In mouse spinal cord injury, Mylip was identified as a gene that is differentially expressed at 3-and 7-days post-injury, suggesting it may be a new potential player in spinal cord repair [4]. In a study on Chinese pregnant women, the polymorphism of MYLIP rs3757354 was associated with the risk of early-onset preeclampsia [5].

In conclusion, Mylip is essential in cholesterol metabolism by regulating the LDL receptor. Its functions also extend to cancer cell growth regulation in prostate cancer and potentially to spinal cord repair and preeclampsia risk. Studies using various models, though not specifically KO/CKO mouse models in these references, have provided insights into Mylip's role in these biological processes and disease conditions.

References:

1. Lindholm, Dan, Bornhauser, Beat C, Korhonen, Laura. 2009. Mylip makes an Idol turn into regulation of LDL receptor. In Cellular and molecular life sciences : CMLS, 66, 3399-402. doi:10.1007/s00018-009-0127-y. https://pubmed.ncbi.nlm.nih.gov/19688294/

2. Zelcer, Noam, Hong, Cynthia, Boyadjian, Rima, Tontonoz, Peter. 2009. LXR regulates cholesterol uptake through Idol-dependent ubiquitination of the LDL receptor. In Science (New York, N.Y.), 325, 100-4. doi:10.1126/science.1168974. https://pubmed.ncbi.nlm.nih.gov/19520913/

3. Ito, Saya, Ueno, Akihisa, Ueda, Takashi, Okihara, Koji, Ukimura, Osamu. 2018. CNPY2 inhibits MYLIP-mediated AR protein degradation in prostate cancer cells. In Oncotarget, 9, 17645-17655. doi:10.18632/oncotarget.24824. https://pubmed.ncbi.nlm.nih.gov/29707137/

4. Martins, Isaura, Neves-Silva, Dalila, Ascensão-Ferreira, Mariana, Barbosa-Morais, Nuno L, Saúde, Leonor. 2023. Mouse Spinal Cord Vascular Transcriptome Analysis Identifies CD9 and MYLIP as Injury-Induced Players. In International journal of molecular sciences, 24, . doi:10.3390/ijms24076433. https://pubmed.ncbi.nlm.nih.gov/37047406/

5. Wang, He, Ma, Lingyu, Pan, Xuefeng, Du, Zhaoli, Chen, Ying. 2020. Novel associations of SNPs MYLIP rs3757354 and ABCA1 2230806 gene with early-onset-preeclampsia: A case-control candidate genetic study. In Pregnancy hypertension, 23, 185-190. doi:10.1016/j.preghy.2020.12.005. https://pubmed.ncbi.nlm.nih.gov/33450693/