Unsurprisingly, defects in CA2 activity lead to osteopetrosis and extra-skeletal disturbances including renal tubular acidosis and cerebral calcification, reminiscent of the clinical features observed in patients harboring mutations in TCIRG1. At the same time, CA2 stabilizes intracellular pH (pHi) and alkalinisation in OCs through the liberation of HCO3– ions. Here, CA2 is linked to renal tubular acidosis.