Inorganic pyrophosphate (PPi) is continuously produced as a result of ATP-utilising biosynthesis of protein, RNA, and DNA. Inorganic pyrophosphatase (PPase) catalyses the hydrolysis of PPi into two orthophosphates (Pi) thereby minimizing the cellular level of PPi and driving otherwise reversible reactions in the direction of PPi generation. Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) is a dimeric protein, binding a Mg2+ in each subunit which can mediate the hydrolysis of PPi to 2xPi (Yokoi et al. 2003, Koike et al. 2006). LHPP is expressed in thyrocytes, located in the cytosol and nucleoplasm. In addition, LHPP is more prominently expressed in hyperfunctional states of the thyroid, such as in Graves disease and autonomously functional thyroid nodule (AFTN) (Koike et al. 2006).
