LNPEP Gene: Function, Expression, and Clinical Significance

LNPEP encodes leucyl/cystinyl aminopeptidase, a zinc-dependent aminopeptidase that cleaves N-terminal cysteine or leucine residues. It is also known as insulin-regulated aminopeptidase (IRAP) and oxytocinase. The enzyme is involved in peptide hormone processing, including degradation of oxytocin, vasopressin, and angiotensin III. It is highly expressed in placenta, kidney, and brain, and plays roles in glucose metabolism, blood pressure regulation, and immune function.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Peptide hormone metabolism (Reactome R-HSA-422085)

• Insulin receptor recycling (Reactome R-HSA-77387)

• Angiotensin III degradation (Reactome R-HSA-2022377)

The LNPEP protein (UniProt Q9UI6) is a type II transmembrane zinc metallopeptidase of the M1 family. It is composed of 1025 amino acids with a molecular weight of ~117 kDa. The protein contains a short N-terminal cytoplasmic domain, a transmembrane helix, and a large extracellular catalytic domain. It functions as a homodimer and is localized to the plasma membrane, endosomes, and lysosomes. In adipocytes and muscle cells, it colocalizes with GLUT4 vesicles and is translocated to the plasma membrane in response to insulin, where it degrades peptide substrates such as oxytocin, vasopressin, and angiotensin III.