NAMPT (nicotinamide phosphoribosyltransferase; HGNC:30092, NCBI Gene ID 10135) is a human locus mapped to chromosome band 7q22.3 that encodes homodimeric intracellular iNAMPT enzyme & extracellular eNAMPT/Visfatin adipokine (491 aa; EC 2.4.2.12). NAMPT acts in rate-limiting step of the mammalian NAD+ salvage pathway (Nicotinamide + PRPP to NMN), together with NADSYN1 (De Novo NAD+ Synthetase 1 Gene), CD38 (Major Cellular NAD+ Hydrolase Gene), and SIRT1 (NAD+-Dependent Deacetylase Gene). Encodes nicotinamide phosphoribosyltransferase, the rate-limiting enzyme recycling nicotinamide into NMN in the mammalian NAD+ salvage pathway.
Genomic Organization & Cytogenetic Locus: 11-exon gene on chromosome 7q22.3 whose promoter contains canonical E-box elements bound by the core circadian heterodimer CLOCK:BMAL1 and is induced by exercise-activated AMPK.
Cellular & Tissue Expression Profile: Ubiquitously expressed across metabolically active tissues—highest in hepatic hepatocytes, skeletal muscle fibers, cardiac myocytes, brown adipocytes, and proliferating lymphocytes—both as intracellular iNAMPT and as a secreted circulating form (eNAMPT / visfatin / PBEF).
Molecular Function & Pathways
Biochemical & Physiological Mechanism: Catalyzes the ATP-coupled condensation of nicotinamide (NAM, generated as the byproduct of NAD+-consuming sirtuins SIRT1–SIRT7, PARP1, and CD38) with 5-phosphoribosyl-1-pyrophosphate (PRPP) to synthesize nicotinamide mononucleotide (NMN), which NMNAT1–3 then adenylates into NAD+; because CLOCK:BMAL1 drives rhythmic NAMPT transcription and NAD+-activated SIRT1 deacetylates BMAL1/PER2, NAMPT forms the metabolic oscillator of the mammalian circadian clock.
Clinical & Therapeutic Significance
Human Genetic Variants & Disease Phenotypes: Tissue iNAMPT protein levels and circulating eNAMPT-containing extracellular vesicles decline progressively with chronological aging in skeletal muscle, adipose tissue, and hypothalamus, driving systemic NAD+ depletion and impairing mitochondrial sirtuin (SIRT1/SIRT3) and DNA repair (PARP1) capacity.
Therapeutic & Clinical Pharmacology: While small-molecule allosteric NAMPT activators (such as SBI-797812 and NAT) and downstream NMN/NR precursors aim to restore NAD+ homeostasis in metabolic and aging disorders, potent NAMPT inhibitors (FK866 / daporinad, OT-82) selectively starve NAD+-addicted hematologic and solid malignancies.