NAPRT (nicotinate phosphoribosyltransferase) catalyzes the first step in NAD biosynthesis via the Preiss-Handler pathway, converting nicotinic acid and 5-phospho-D-ribose 1-phosphate to beta-nicotinate D-ribonucleotide in an ATP-dependent manner 123. This enzymatic function helps prevent cellular oxidative stress by maintaining NAD+ levels 1. NAPRT expression varies widely across human tissues and tumor types 4, with expression patterns critically determining therapeutic response. In cancer contexts, NAPRT expression confers resistance to NAMPT inhibitors by providing an alternative NAD biosynthetic route 5. Conversely, NAPRT silencing through epigenetic hypermethylation—induced by oncogenic drivers like mutant PPM1D in gliomas or fumarate accumulation in FH-deficient renal carcinoma—creates therapeutic vulnerabilities exploitable by NAMPT inhibition 67. Dual NAMPT and NAPRT inhibition demonstrates synergistic anti-tumor efficacy across multiple cancer types 859. Beyond cancer, NAPRT modulation affects ferroptosis regulation in cardiac tissue, where downregulation protects cardiomyocytes from ferroptosis-induced injury 10. Thus, NAPRT functions as both a rate-limiting NAD biosynthetic enzyme and an emerging biomarker for personalized cancer therapy strategies.