Nicotinamide phosphoribosyltransferase

Nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to produce nicotinamide mononucleotide, a key intermediate in NAD biosynthesis (UniProt: P43490). As the rate-limiting enzyme in mammalian NAD synthesis, NAMPT plays a central role in cellular energetics and NAD-dependent processes. The protein also exists in a secreted form that functions as a cytokine and adipokine with immunomodulating properties, and participates in circadian clock regulation through NAD-dependent modulation of the CLOCK-BMAL1 complex and SIRT1 (UniProt: P43490).

NAMPT is broadly expressed and regulates NAD availability across multiple tissues and metabolic pathways. No specific disease associations are annotated in UniProt, though NAD metabolism has been implicated in numerous age-related and neurodegenerative processes.

In Alzheimer's Disease, NAMPT is upregulated in human post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics), with a mean log2 fold-change of 0.86. This elevation suggests altered NAD metabolism may be relevant to AD pathogenesis, though the functional consequences of increased NAMPT expression in AD brain remain to be clarified.