Pkd1, encoding Polycystin-1, is a gene of great significance. Mutations in Pkd1, along with Pkd2, are major causes of autosomal dominant polycystic kidney disease (ADPKD), one of the most common monogenetic disorders. Pkd1-Pkd2 complex forms a non-canonical transient receptor potential (TRP) channel architecture, which is crucial for normal physiological functions [1].

In ADPKD, kidney cyst formation occurs when Pkd1 dosage falls below a critical threshold. Eliminating the miR-17 binding element in the 3'-UTR of Pkd1 mRNA can improve mRNA stability, raise Polycystin-1 levels, and alleviate cyst growth in cellular, ex vivo, and mouse PKD models. Pkd1 haploinsufficiency in mice accelerates liver regeneration after partial hepatectomy and protects against fatty liver disease, selectively increasing mTOR signaling without SREBP-1c activation [2,3]. In the lymphatic vascular system of mice, Pkd1 genetically interacts with Wnt5a to control lymphatic vascular morphogenesis, with loss of either showing similar lymphatic defects [4].

In conclusion, Pkd1 is essential in maintaining normal physiological functions, especially in relation to kidney, liver, and lymphatic vascular systems. Gene-targeted strategies and knockout mouse models have been instrumental in understanding its role in diseases like ADPKD, fatty liver disease, and lymphatic development, providing insights for potential therapeutic interventions.