Catalyzes the synthesis of phosphoribosylpyrophosphate (PRPP) that is essential for nucleotide synthesis. ATP + D-ribose 5-phosphate = 5-phospho-alpha-D-ribose 1-diphosphate + AMP + H(+) Activated by magnesium and inorganic phosphate. Inhibited by ADP and GDP (PubMed:7593598). Metabolic intermediate biosynthesis; 5-phospho-alpha-D-ribose 1-diphosphate biosynthesis; 5-phospho-alpha-D-ribose 1-diphosphate from D-ribose 5-phosphate (route I): step 1/1. Homodimer. The active form is probably a hexamer composed of 3 homodimers. Phosphoribosyl pyrophosphate synthetase I deficiency is a rare condition caused by mutations in PRPS1 that lead to variable disease phenotypes including optic atrophy, retinitis pigmentosa, ataxia, peripheral neuropathy and hearing loss. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. A mutation in PRPS1 has been found in a patient with a phenotype that bridges that of PRSPS1 superactivity and ARTS syndrome with uric acid overproduction without gout but with recurrent infections, sensorineural hearing loss and motor neuropathy. The intermediate phenotype may be because Leu-142 variant affects both allosteric sites that are involved in inhibition of PRPS1 and the ATP-binding site, which suggests that this substitution can result both in a gain-of-function and loss-of-function of PRPP synthetase. Belongs to the ribose-phosphate pyrophosphokinase family.