PRPSAP1 (phosphoribosyl pyrophosphate synthetase associated protein 1) functions as a negative regulator of nucleotide biosynthesis by associating with phosphoribosyl pyrophosphate synthetase (PRPS) enzymes. Beyond its canonical role in nucleotide metabolism, PRPSAP1 plays an unexpected role in chr17 assembly independent of nucleotide production; depletion of PRPSAP1 limits histone availability and disrupts chr17 formation, revealing coordination between nucleotide metabolism and histone maturation 1. Regarding disease relevance, PRPSAP1 expression alterations associate with multiple pathological conditions. Exosomal PRPSAP1 in plasma shows promise as a preoperative biomarker for microvascular invasion in hepatocellular carcinoma, with significantly elevated levels in patients with extensive microvascular invasion 2. PRPSAP1 expression is downregulated in sub-lethally heat-treated hepatoma cells, suggesting involvement in cancer cell recurrence after radiofrequency ablation 3. A genetic variant near PRPSAP1 (rs66459581) shows suggestive association with high-grade serous ovarian carcinoma in women of African ancestry 4. Additionally, PRPSAP1 mRNA levels are negatively correlated with insulin-mediated glucose disposal rates in non-diabetic insulin-resistant individuals, implicating it as a candidate susceptibility gene for insulin resistance 5.