PDZK1 is a multi-domain scaffold protein that plays crucial roles in membrane protein regulation and cellular homeostasis across diverse tissues. As a scaffold protein, PDZK1 connects plasma membrane proteins to regulatory components, particularly in epithelial cell apical domains 1. The protein regulates multiple transporters including urate transporters, where it promotes ABCG2 localization to brush border membranes to facilitate intestinal urate excretion 1. PDZK1 variants show significant association with gout susceptibility in Japanese populations, likely through regulation of urate transporter functions 2. In HDL metabolism, PDZK1 is essential for maintaining hepatic SR-BI receptor levels and controlling HDL cholesterol homeostasis, with all four PDZ domains required for normal SR-BI expression and function 34. Beyond metabolic functions, PDZK1 exhibits protective roles against cellular senescence through mitochondrial function regulation, particularly in chondrocytes where it prevents mechanical overload-induced osteoarthritis by targeting the Hmgcs2 pathway 5. In retinal pigment epithelium, PDZK1 protects against diabetic retinopathy by regulating the 14-3-3ε-mTOR axis to reduce oxidative stress and enhance autophagy 6. Additionally, PDZK1 functions as a tumor suppressor in triple-negative breast cancer by promoting EGFR degradation and sensitizing cells to erlotinib treatment 7.