PRNP encodes the prion protein, a glycoprotein with multiple cellular functions and prominent disease associations. The protein's primary physiological role remains incompletely characterized but likely involves neuronal development, synaptic plasticity, and myelin maintenance 1. PRNP may promote myelin homeostasis through ADGRG6 receptor signaling and participates in copper and iron homeostasis. The protein associates with glypican-1 via heparan sulfate chains to localize to lipid rafts, where it facilitates copper-mediated signaling 2. Pathologically, PRNP is central to prion diseases—a group of fatal neurodegenerative disorders caused by conformationally abnormal prion protein (PrP^Sc). These diseases occur in three forms: sporadic Creutzfeldt-Jakob disease (sCJD, most common), genetic forms (caused by PRNP mutations including those at codons 102, 105, 117, and others), and acquired forms (kuru, variant CJD) 13. Genetic susceptibility is influenced by PRNP codon 129 polymorphisms; variant CJD patients universally share identical genotypes at this position 4. Genetic prion diseases show remarkable phenotypic variability, progressing from dysautonomia and neuropathy to frontotemporal dementia 1. Despite extensive clinical trials, no disease-modifying treatments currently provide survival benefit 1. Recently, PRNP expression has emerged in oncology: elevated PRNP promotes lung cancer metastasis through c-Jun-miR-193b-3p axis regulation 5, while PRNP downregulation in breast cancer correlates with improved prognosis and enhanced ferroptosis sensitivity 2.