Lnpep, also known as insulin-responsive aminopeptidase, encodes a zinc-dependent aminopeptidase. It is involved in multiple biological processes, including the renin-angiotensin system [3,4,5]. LNPEP also has a role in vesicle-mediated transport and class I MHC-mediated antigen processing and presentation [7]. Additionally, it is a key regulator of oxytocin [6].

In psoriasis, a missense variant in LNPEP (rs2303138) was associated with the disease, and LNPEP was significantly downregulated in psoriatic lesions. Pathway analysis indicated its involvement in the renin-angiotensin system, suggesting shared mechanisms between psoriasis, hypertension, and diabetes [5]. In ovarian cancer, high LNPEP expression was associated with poor prognosis, and it was identified as an independent prognostic factor. Bioinformatics analyses showed its co-expressed genes were related to immune-related pathways, and its expression was strongly correlated with immune infiltration levels [7]. In hepatocellular carcinoma, the AR/circ-LNPEP/miR-532-3p/RAB9A signaling axis was involved in hypoxia-induced cell invasion, with AR reducing circ-LNPEP expression to inhibit cell invasion [2]. In the context of autism spectrum disorder, an imbalance in the expression of CD38 and LNPEP could potentially lead to alterations in oxytocin and vasopressin concentrations [1].

In conclusion, LNPEP is crucial in multiple biological processes and disease conditions. Its involvement in the renin-angiotensin system, immune-related functions, and its role in regulating hormone concentrations highlight its importance. Research on LNPEP in various diseases such as psoriasis, ovarian cancer, hepatocellular carcinoma, and autism spectrum disorder, provides insights into disease mechanisms and potential therapeutic targets.

References:

1. Wilczyński, Krzysztof Maria, Auguściak-Duma, Aleksandra, Stasik, Aleksandra, Kawalec, Alicja, Janas-Kozik, Małgorzata. 2023. Association of OXTR, AVPR1a, LNPEP, and CD38 Genes' Expression with the Clinical Presentation of Autism Spectrum Disorder. In Current issues in molecular biology, 45, 8359-8371. doi:10.3390/cimb45100527. https://pubmed.ncbi.nlm.nih.gov/37886970/

2. Ouyang, Xiwu, Yao, Lei, Liu, Guodong, Gong, Liansheng, Xiao, Yao. 2021. Loss of androgen receptor promotes HCC invasion and metastasis via activating circ-LNPEP/miR-532-3p/RAB9A signal under hypoxia. In Biochemical and biophysical research communications, 557, 26-32. doi:10.1016/j.bbrc.2021.02.120. https://pubmed.ncbi.nlm.nih.gov/33862456/

3. Li, Don T, Habtemichael, Estifanos N, Bogan, Jonathan S. 2019. Vasopressin inactivation: Role of insulin-regulated aminopeptidase. In Vitamins and hormones, 113, 101-128. doi:10.1016/bs.vh.2019.08.017. https://pubmed.ncbi.nlm.nih.gov/32138946/

4. Paladini, Fabiana, Fiorillo, Maria Teresa, Tedeschi, Valentina, Mattorre, Benedetta, Sorrentino, Rosa. 2020. The Multifaceted Nature of Aminopeptidases ERAP1, ERAP2, and LNPEP: From Evolution to Disease. In Frontiers in immunology, 11, 1576. doi:10.3389/fimmu.2020.01576. https://pubmed.ncbi.nlm.nih.gov/32793222/

5. Cheng, Hui, Li, Yang, Zuo, Xian-Bo, Sun, Liang-Dan, Zhang, Xue-Jun. 2013. Identification of a missense variant in LNPEP that confers psoriasis risk. In The Journal of investigative dermatology, 134, 359-365. doi:10.1038/jid.2013.317. https://pubmed.ncbi.nlm.nih.gov/23897274/

6. Diel de Amorim, Mariana, Dong, Lynn, Byron, Michael, Saleh, Tarek, Card, Claire. 2023. Characterization of serum and tissue oxytocinase and tissue oxytocin in the pregnant and non-pregnant mare. In Scientific reports, 13, 4616. doi:10.1038/s41598-023-31540-9. https://pubmed.ncbi.nlm.nih.gov/36944665/

7. Ma, Qian, Chang, Lei, Wang, Wenwen, Gu, Zhuoyu, Ge, Xin. 2023. Leucyl and Cystinyl Aminopeptidase as a Prognostic-Related Biomarker in OV Correlating with Immune Infiltrates. In Pharmacogenomics and personalized medicine, 16, 551-568. doi:10.2147/PGPM.S400145. https://pubmed.ncbi.nlm.nih.gov/37293607/