Nicotinamide phosphoribosyltransferase (NAMPT) (NAMPT)

Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme in the NAD+ salvage pathway, essential for keratinocyte homeostasis (UniProt P43490). It converts nicotinamide to nicotinamide mononucleotide (NMN), maintaining levels of NAD+ and NADP+ which are critical for lipid biosynthesis and redox balance (Tanno et al., 2000, British Journal of Dermatology). In the epidermis, elevated NAD+ levels stimulate the expression of serine palmitoyltransferase, leading to increased ceramide synthesis and improved skin barrier function (PubMed PMID: 10971324). Furthermore, the NAMPT-mediated pathway regulates inflammatory mediator production by modulating sirtuin activity and inhibiting cytokines like IL-1, IL-6, and TNF-alpha (NCBI PMC2885954). This metabolic axis is a therapeutic target for inflammatory skin diseases such as atopic dermatitis and psoriasis, primarily through the use of nicotinamide to boost barrier lipids and suppress inflammation (StatPearls: Niacinamide). While NAMPT inhibitors like FK866 are explored in oncology to deplete NAD+, the focus in dermatology remains on pathway activation to restore skin health.

Other names

VisfatinPre-B-cell colony-enhancing factor 1PBEF1NAD+ salvage pathwayKeratinocyte NAD+ metabolic pathwayKeratinocyte NAD+/NADP+ metabolic enzymes and downstream pathways regulating ceramide synthesis and inflammatory mediator production

Activation of the NAD+ salvage pathway via precursor supplementation to enhance ceramide synthesis and barrier function; or competitive inhibition of NAMPT to induce apoptosis in metabolic-sensitive cells.