Anpep, also known as alanyl aminopeptidase, membrane or CD13, is an ectopeptidase. It is involved in various physiological functions such as proliferation, differentiation, migration, angiogenesis, invasion, and metastasis. It is part of the renin-angiotensin system (RAS), where it converts angiotensin (Ang) III to Ang IV [3].

In esophageal adenocarcinoma, elevated expression of ANPEP/CD13 indicates shorter survival of patients and a more invasive phenotype of cancer cells in vitro [1]. In gallbladder squamous cell/adenosquamous carcinomas and adenocarcinomas, a marked reduction in ANPEP levels was associated with larger tumors, higher TNM staging, invasion, and metastasis [4]. In the context of non-alcoholic fatty liver disease, ANPEP is strongly associated with the disease, potentially having a role in extracellular matrix remodeling in fibrosis [2]. Polymorphisms of the ANPEP gene are associated with microvascular complications of type 2 diabetes, such as diabetic retinopathy and nephropathy [5].

In summary, Anpep is crucial in multiple biological processes and is associated with various diseases including cancer, liver disease, and diabetes-related microvascular complications. Its role in these diseases highlights its potential as a biomarker and therapeutic target, although further research, such as that enabled by gene knockout models, could provide more in-depth understanding of its functions [1,2,4,5].

References:

1. Goltsov, Alexei A, Maru, Dipen M, Katkhuda, Riham, Futreal, P Andrew, Hofstetter, Wayne L. 2023. ANPEP/CD13 Expression as a Marker of Lymphovascular Invasion and Survival in Esophageal Adenocarcinoma. In The Annals of thoracic surgery, 118, 241-251. doi:10.1016/j.athoracsur.2023.09.036. https://pubmed.ncbi.nlm.nih.gov/37806335/

2. Niu, Lili, Geyer, Philipp E, Wewer Albrechtsen, Nicolai J, Hofmann, Susanna M, Mann, Matthias. 2019. Plasma proteome profiling discovers novel proteins associated with non-alcoholic fatty liver disease. In Molecular systems biology, 15, e8793. doi:10.15252/msb.20188793. https://pubmed.ncbi.nlm.nih.gov/30824564/

3. Kim, Jong-Heon, Afridi, Ruqayya, Cho, Eunji, Ryu, Hoon, Suk, Kyoungho. 2022. Soluble ANPEP Released From Human Astrocytes as a Positive Regulator of Microglial Activation and Neuroinflammation: Brain Renin-Angiotensin System in Astrocyte-Microglia Crosstalk. In Molecular & cellular proteomics : MCP, 21, 100424. doi:10.1016/j.mcpro.2022.100424. https://pubmed.ncbi.nlm.nih.gov/36220603/

4. Liu, Ziru, Yang, Zhulin, Xiong, Li, Zou, Qiong, Yuan, Yuan. 2020. ACO2 and ANPEP as novel prognostic markers for gallbladder squamous cell/adenosquamous carcinomas and adenocarcinomas. In International journal of clinical oncology, 25, 1346-1355. doi:10.1007/s10147-020-01651-8. https://pubmed.ncbi.nlm.nih.gov/32249333/

5. Korvyakova, Ya E, Azarova, I E, Markina, D D, Solodilova, M A, Polonikov, A V. 2024. Polymorphisms of ANPEP Gene Are Associated with Microvascular Complications of Type 2 Diabetes. In Bulletin of experimental biology and medicine, 178, 79-85. doi:10.1007/s10517-024-06286-7. https://pubmed.ncbi.nlm.nih.gov/39576474/