Federal Grant Award Summary

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) awarded The Regents of the University of California, San Francisco $790,063 under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847) on March 1, 2026, with a completion date of December 31, 2030. This Project Grant funds research to functionally characterize and classify pathogenic missense mutations in polycystin-1 (PC1), a protein whose mutations account for 80% of autosomal dominant polycystic kidney disease (ADPKD) cases. The research deliverables include quantitative analysis of how PC1 variants affect protein expression, trafficking, and channel function; identification of variant susceptibility to rescue through temperature shift or small molecule interventions; and determination of how small molecules restore defective polycystin function and affect cystogenesis using a kidney organoid system.

The project addresses a significant clinical gap, as ADPKD is the most common monogenic cause of kidney failure globally, accounting for 10% of all kidney failure cases. By elucidating the fundamental mechanisms by which pathogenic PC1 mutations cause disease and classifying variants by molecular mechanism, the research aims to enable rational development of therapeutics for ADPKD comparable to recent advances achieved in cystic fibrosis treatment.