Neurolysin, mitochondrial (NLN)

Neurolysin, mitochondrial (NLN) is a zinc-dependent metallopeptidase enzyme of the M3 family, encoded by the NLN gene. It hydrolyzes short bioactive peptides (typically 5–17 amino acids), including important signaling molecules such as neurotensin, angiotensins, bradykinin, and substance P, thereby modulating neurochemical and cardiovascular processes. NLN is distributed across tissues with high abundance in brain and liver, localizing to the cytosol, mitochondria, plasma membrane, and extracellular space depending on cell type. Structurally, it features a dumbbell-shaped central cavity with a zinc-containing catalytic site in a deep channel, conferring selectivity for small peptides via substrate channel gating. Neurolysin plays vital physiological roles in neuropeptide cleavage, pain perception, blood pressure regulation, and mitochondrial respiratory chain dynamics. Aberrant expression or function of NLN is implicated in diseases such as acute myeloid leukemia, various neurological disorders, cardiovascular disease, and cancer. Ongoing research aims to develop small molecule modulators for therapeutic applications, though the enzyme's diverse physiological roles present challenges for selective targeting

Other names

AGTBPKIAA1226MEPEP24.16MOPAngiotensin-binding proteinMicrosomal endopeptidaseMitochondrial oligopeptidase MNeurotensin endopeptidase

Competitive inhibition at the active site (by peptide inhibitors such as dynorphin A(1–13)), Allosteric inhibition (by small molecules), Enzyme activation/inhibition affecting peptide substrate turnover (e.g., neurotensin, angiotensin, bradykinin modulation)