The thick ascending limb of the Loop of Henle (TAL) plays a crucial role in the modulation of the homeostatic mechanisms involved in renal physiology. The TAL is responsible for reabsorbing at least 30% of the filtered sodium, which is necessary to maintain proper control of the countercurrent mechanism, and therefore maintain the extracellular fluid in equilibrium. The TAL is also critical for divalent cations and acid-base homeostasis.

Sodium reabsorption occurs through transcellular transport mechanisms driven by the Na+-K+-2Cl- cotransporter (NKCC2). This transport is coupled by the recycling of K+ through ROMK1 and the basolateral exit of Cl- by ClC-K channel. This generates a positive transepithelial voltage that allows the paracellular transport of cations by claudins. Calcium reabsorption is also regulated by calcium-sensing receptor (CaSR) and parathyroid hormone receptor type 1 (PTH1R) transporters in the basolateral side. Moreover, Uromodulin (also known as Tamm-Horsfall protein), is a protein that is exclusively expressed in the TAL, and that in recent years has gained attention for its role in the regulation of TAL function, and for its striking effect as a genetic risk factor in the development of chronic kidney disease.

The importance of these, and many other TAL mechanisms are highlighted by the fact that many of the monogenic diseases that affect the kidney target genes that are relevant to these mechanisms.

In this Research Topic, we want to gather recent developments that unravel our current understanding of TAL physiology and regulation. Therefore, this Research Topic welcomes basic, translational, and applied research that grasps the many unanswered and complex questions in TAL physiology. Potential areas of interest may include, but are not limited to:
• Regulation of sodium transport in the TAL 
• Counter-current mechanism
• NKCC2
• Vasopressin
• UMOD
• Regulation of calcium homeostasis (TRPV5, CaSR, Claudins, PTH)
• Regulation of TAL acid-base mechanisms (NHE3, AE2)
• Pathologies of the TAL (Claudinopathies, Bartter Syndrome and UMOD-kidney disease)

We encourage the submission of different article types to this collection, especially reviews, mini-reviews, and original research papers.

For a complete list of article types that can be considered, please follow this link. Even though abstract submission is not mandatory, we encourage all interested researchers to submit an abstract before submitting their manuscript. Abstracts do not have to coincide with the final abstract of the manuscripts.

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Frontiers in Physiology

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