Urea transporters (UTs) UT-As (encoded by Slc14A2) and UT-B (encoded by Slc14A1), are important members of the solute carrier family. They are a group of membrane channel proteins that are selectively permeable to urea. Slc14A1 is considered the key gene determining the Kidd blood group system, and its variants can lead to the loss of Jk antigens, resulting in transfusion-related complications. Additionally, studies have shown that Slc14A1 is closely associated with cancer development and progression, with its expression level and promoter methylation status potentially serving as biomarkers for cancer progression and prognosis. Recent research suggests that UT-B functional deficiency may cause neurodegenerative diseases by accumulating urea in the brain, thereby affecting neuronal function and viability. Mutations of Slc14A2 are linked to hypertension and metabolic syndrome, due to its essential role in maintaining urea homeostasis. This chapter aims to introduce the clinical significance of UT-B and UT-A and highlight their potential roles as diagnostic and therapeutic targets.