A cellular
prion protein (PrPC) is a ubiquitous
cell surface glycoprotein, and its physiological functions have been receiving increased attention. Endogenous PrPC is present in various kidney tissues and undergoes glomerular filtration. In
prion diseases, abnormal
prion proteins are found to accumulate in renal tissues and filtered into urine. Urinary
prion protein could serve as a diagnostic
biomarker. PrPC plays a role in cellular signaling pathways, reno-protective effects, and kidney
iron uptake. PrPC signaling affects mitochondrial function via the ERK pathway and is affected by the regulatory influence of
microRNAs, small molecules, and signaling
proteins. Targeting PrPC in acute and
chronic kidney disease could help improve
iron homeostasis, ameliorate damage from
ischemia/reperfusion injury, and enhance the efficacy of mesenchymal stem/stromal cell or extracellular vesicle-based therapeutic strategies. PrPC may also be under the influence of BMP/Smad signaling and affect the progression of TGF-β-related renal
fibrosis. PrPC conveys TNF-α resistance in some
renal cancers, and therefore, the coadministration of anti-PrPC
antibodies improves
chemotherapy. PrPC can be used to design
antibody-drug conjugates, aptamer-drug conjugates, and customized tissue inhibitors of
metalloproteinases to suppress
cancer. With preclinical studies demonstrating promising results, further research on PrPC in the kidney may lead to innovative PrPC-based therapeutic strategies for renal disease.