SHPK (sedoheptulokinase) is a carbohydrate kinase that catalyzes the phosphorylation of sedoheptulose to sedoheptulose-7-phosphate, functioning as a key regulator of carbon flux in the non-oxidative arm of the pentose phosphate pathway (PPP) 1. The enzyme modulates macrophage activation through control of glucose metabolism and perturbations in PPP metabolism 2. SHPK is localized to the cytoplasm and cytosol, where it influences metabolic processes and cellular responses to inflammatory signals including lipopolysaccharide, interleukin-4, and interleukin-13 2. Clinically, isolated SHPK deficiency is a rare genetic disorder characterized by elevated urinary excretion of erythritol and sedoheptulose 12. The most common cystinosis-causing mutation is a 57-kb deletion on chromosome 17 that eliminates both CTNS and SHPK, with affected patients showing 6-23 fold elevated sedoheptulose in blood spots detectable in the neonatal period 3. SHPK is also emerging as significant in cancer biology; elevated SHPK expression in glioblastoma correlates with worse prognosis and increased cell proliferation, identifying the non-oxidative PPP and SHPK as potential therapeutic targets 4. However, preclinical evidence demonstrates that SHPK deficiency does not impair hematopoietic stem cell transplantation efficacy for cystinosis rescue 2.