iNAMPT

iNAMPT, also known as intracellular nicotinamide phosphoribosyltransferase, is a ubiquitous enzyme that catalyzes the rate‑limiting step in the salvage pathway of nicotinamide adenine dinucleotide (NAD⁺) biosynthesis. The enzyme transfers a phosphoribosyl group from 5‑phosphoribosyl‑1‑pyrophosphate (PRPP) to nicotinamide, forming nicotinamide mononucleotide (NMN), which is subsequently converted to NAD⁺ by NMN adenylyltransferase. In humans, iNAMPT is encoded by the NAMPT gene located on chromosome 7q22.1 and is expressed in most tissues, with particularly high levels in liver, skeletal muscle, and adipose tissue.

Structurally, iNAMPT functions as a homodimer, each subunit containing a catalytic domain that binds PRPP and nicotinamide. The enzyme requires magnesium ions for activity and is regulated by substrate availability, post‑translational modifications such as acetylation, and cellular energy status. Because NAD⁺ is essential for metabolic reactions, DNA repair, and the activity of sirtuins and poly(ADP‑ribose) polymerases, iNAMPT plays a central role in maintaining cellular homeostasis.

Alterations in iNAMPT expression or activity have been linked to metabolic disorders, inflammation, aging, and cancer. Reduced iNAMPT activity contributes to NAD⁺ depletion observed in aged tissues, whereas overexpression is associated with enhanced tumor growth and resistance to chemotherapy. Consequently, iNAMPT is a target for pharmacological intervention; inhibitors such as FK866 (APO866) have entered clinical trials for hematologic malignancies, while NAD⁺‑boosting strategies using NMN or nicotinamide riboside aim to counteract age‑related decline. Ongoing research continues to clarify iNAMPT’s diverse physiological and pathological roles.