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Renalase, FAD-dependent amine oxidase (RNLS)

Target
RNLS
Molecular classification
Enzyme, Monoamine oxidase family (distinct from MAO-A/-B), Flavin adenine dinucleotide (FAD)-dependent oxidase, Secreted protein/hormone, cytokine-like signaling molecule
01

Overview

Renalase is a secreted FAD-dependent amine oxidase enzyme encoded by the RNLS gene, predominantly produced by the kidney and released into the bloodstream. It functions principally in the metabolism of circulating biogenic amines (notably catecholamines), thereby regulating blood pressure, heart rate, and systemic sympathetic tone. Renalase also catalyzes the oxidation of atypical NAD(P)H isomers, alleviating primary metabolism enzyme inhibition. Beyond its enzymatic roles, renalase acts as a growth/survival factor (cytokine-like), activates cell signaling through PI3K and MAPK pathways, and is implicated in cancer cell survival. Decreased renalase levels are associated with ESRD and increased cardiovascular morbidity. The physiological and pathophysiological footprint spans cardiovascular, renal, metabolic, and oncologic disease, with several lines of research exploring therapeutic manipulation and biomarker utility.

Other names
RenalaseRNLSC10orf59FLJ11218Monoamine oxidase-CMAO-Calpha-NAD(P)H oxidase/anomerase
02

Mechanism of action

Recombinant renalase lowers plasma catecholamine levels and blood pressure, primarily by catabolism of dopamine, epinephrine, norepinephrine and through PI3K/MAPK signaling. Cytoprotective effect mediated by cell signaling pathways independent of enzymatic function. Dopaminergic agonists affect renalase expression via PKC signaling.

03

Biological functions

Metabolism of catecholamines (dopamine, epinephrine, norepinephrine—especially in vitro/in vivo models)Oxidation of isomeric forms of NAD(P)H (specifically 6- and 2-dihydroNAD(P))Regulation of systemic blood pressure and cardiac contractilityCellular cytoprotection (PI3K and MAPK pathway activation)Putative cytokine/survival and growth factor for certain tissues, including tumorsInfluences phosphate and sodium homeostasis
04

Disease associations

Cardiovascular disease (hypertension, cardiac hypertrophy, ventricular dysfunction)Renal disease, especially end-stage renal disease (ESRD)Metabolic disease (roles in lipid and glucose metabolism)Cancer (promotes tumor survival and growth)Potential relevance in neurodegenerative diseases via catecholamine metabolism
05

Safety considerations

Modulation of catecholamine metabolism may precipitate cardiovascular effects (hypotension, cardiac dysregulation)Unknown effects of long-term renalase administration or inhibition (e.g., impact on intracellular signaling and metabolism)Tumor-promoting activity in cancer contexts poses a risk for therapeutic use
06

Interacting drugs

Recombinant renalase (experimental)

2 more in the full profile.

07

Biomarkers

Renalase protein level in plasma (possible marker for kidney and cardiovascular disease severity)RNLS gene single-nucleotide polymorphisms (e.g., rs2296545 Glu37Asp linked to cardiometabolic risk)Polymorphisms in RNLS gene as predictors of cardiac hypertrophy and renal outcomes

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