Anpep, also known as alanyl aminopeptidase, membrane or CD13, is a component of the renin-angiotensin system (RAS) and has functions such as converting angiotensin (Ang) III to Ang IV in the brain during neuroinflammation [2]. It may also be involved in extracellular matrix remodeling in fibrosis [4].

In esophageal adenocarcinoma (EAC), elevated ANPEP/CD13 expression indicates shorter survival of patients and a more invasive phenotype of cancer cells in vitro. Down-regulation of its expression reduces colony formation, migration, and invasion of FLO-1 EAC cells, while overexpression in SKGT4 EAC cells increases these properties [1].

In gallbladder squamous cell/adenosquamous carcinomas and adenocarcinomas, a marked reduction in ANPEP levels was observed in cancer tissues relative to normal adjacent tissue or benign lesions. Lack of ANPEP was correlated with larger tumors, higher TNM staging, invasion, metastasis, and decreased overall survival [3].

Polymorphisms in the ANPEP gene are associated with microvascular complications of type 2 diabetes, such as diabetic retinopathy and nephropathy [5].

In conclusion, Anpep plays important roles in multiple disease conditions, including cancer and diabetes-related microvascular complications. Its functions in these diseases are mainly revealed through studies on gene expression changes and their associations with disease phenotypes. Although no KO/CKO mouse model-based findings are present in the given references, these studies on human samples still provide valuable insights into the role of Anpep in disease processes.