Acid-base homeostasis by the kidney is maintained through proximal tubular reclamation of filtered bicarbonate and the excretion of the daily acid load by collecting duct type A intercalated cells. The impairment of either process results in renal tubular acidosis (RTA), a group of disorders characterized by a reduced net acid excretion and a persistent hyperchloremic, non–anion gap metabolic acidosis. The primary or hereditary forms of proximal (pRTA) and distal renal tubular acidosis (dRTA) have received increased attention because of advances in the understanding of the molecular mechanism, whereby mutations in the main proteins involved in acid-base transport result in either reduced bicarbonate reabsorption or reduced H+ secretion and impaired acid excretion. dRTA is characterized by reduced net acid excretion and an inability to lower urine pH despite severe acidemia (but minimal HCO3– wastage). pRTA (type 2), by contrast, is characterized by marked HCO3– wastage but preserved ability to lower urine pH when plasma HCO3– (and therefore filtered HCO3–) is below a certain threshold. In children with dRTA, growth retardation caused by chronic metabolic acidosis is the key manifestation but is fully reversible with appropriate alkali therapy if initiated early in life. A striking manifestation of many patients with dRTA is the development of severe hypokalemia that may cause muscle paralysis. In this review, we discuss these types of hereditary RTA and the mechanisms involved in the genesis of these inherited tubular disorders. This review contains 5 figures, 1 table, and 103 references. Key words: Proximal renal tubular acidosis (pRTA), Distal renal tubular acidosis (dRTA), Hyperchloremic, non–anion gap metabolic acidosis, Hypokalemia, Fractional HCO3– excretion, Urinary gap, Fanconi Syndrome.ATP6V1B1 and ATP6V0A4 gene mutations . Intercalated cells ,