SPRN (shadow of prion protein) is a prion-like gene located on chromosome 10 that encodes the Shadoo (Sho) protein, a structural and functional homolog of the prion protein (PrP) 1. The protein exhibits neuroprotective activity similar to PrP(C) and is hypothesized to act as a biological modulator of normal and abnormal PrP functions 2. SPRN is highly expressed in brain tissue with lower expression in testis and lung 1, and contains an evolutionarily conserved alanine-rich sequence analogous to the amyloidogenic region in PrP 3. Genetically, SPRN functions as a non-PRNP modifier of prion disease susceptibility. SPRN polymorphisms, particularly in the coding sequence and promoter regions, have been associated with variant and sporadic Creutzfeldt-Jakob disease (CJD) in humans and classical scrapie susceptibility in sheep 45. A specific polymorphism causing deletion of two alanines correlates with scrapie susceptibility in ovine populations 4. However, in mice, SPRN shows limited variation across strains and does not substantially influence prion disease incubation time 2, suggesting species-dependent effects. Clinically, SPRN represents an important genetic modifier in prion disease pathogenesis, complementing PRNP-based genetic analysis and potentially informing disease susceptibility screening and mechanistic understanding of transmissible spongiform encephalopathies 5.