The kidney plays quite an important role in the regulation of acid-base homeostasis. The dysfunction of renal acid-base regulation causes diseases such as developmental disorder, bone malformation, calcification of eye and brain, etc. In the kidney, this regulation is performed, to a considerable part, in the proximal tubule of the nephron. In the luminal side the key player is sodium-proton exchanger type 3 (NHE3), whereas sodium-bicarbonate cotransporter (NBCe1) plays the critical role in the basolateral side. In the cytoplasm there is carbonic anhydrase type 2 (CAII) that intermediates the conversion of CO₂/ . Interestingly, in human, mutations have been found in NBCe1 and CAII but not in NHE3 so far. Mutations of NBCe1 lead to severe proximal renal tubular acidosis (pRTA) and other systemic manifestations. In animal model studies, however, the relative contribution of NHE3 to proximal tubule functions remains controversial. Recently, V-ATPase with renal specific subunits is suggested to have some roles in the regulation of proximal tubule functions. In this review, we will discuss the regulation of acid-base transport in the proximal tubule and the updates.