 The study shows that the protein-fibrosistin polyductin, FPC, undergoes complex proteolytic processing in developing kidneys and generates three soluble C-terminal fragments. One of these fragments, ICD-15, contains a mitochondrial targeting sequence at its end terminus, facilitating its translocation into mitochondria. This enhances mitochondrial respiration in renal epithelial cells and partially restores impaired mitochondrial function caused by FPC loss. The study also shows that FPC inactivation leads to abnormal ultrastructural morphology of mitochondria in kidney tubules without cyst formation, and significantly exacerbates renal cystogenesis and triggers severe pancreatic cystogenesis in a PKD1 mouse mutant. Deleting ICD-15 enhances renal cystogenesis without inducing pancreatic cysts in PKD1v, the mice, revealing a direct link between FPC and a mitochondrial pathway through ICD-15 cleavage, crucial for cystogenesis mechanisms. This article was authored by Rebecca V. Walker, Qin Yao, Hang Xiu Aixiu, and others. We are article.tv, links in the description below.