Water cannot escape from this region of the loop. The thick ascending limb plays a vital role in the defense of extracellular fluid volume, urine concentration, calcium and magnesium homeostasis, bicarbonate and ammonium homeostasis, and urinary protein composition in human renal physiology. The study of this nephron segment's molecular physiology and pathology has advanced dramatically over the last decade. This review will focus on these advancements, focusing on the most recent ones. This segment is also impermeable, which means water cannot escape from this loop section.