Bisphosphate nucleotidase 2 (BPNT2), a molecular target of lithium, regulates chondroitin sulfation patterns in the cerebral cortex and hippocampus.

Bisphosphate nucleotidase 2 (BPNT2) is a member of a family of phosphatases that are directly inhibited by lithium, the first-line medication for bipolar disorder. BPNT2 is localized to the Golgi, where it metabolizes the by-products of glycosaminoglycan sulfation reactions. BPNT2-knockout mice exhibit impairments in total-body chondroitin-4-sulfation which lead to abnormal skeletal development (chondrodysplasia).

Sulfation of glycosaminoglycans depends on the catalytic activity of lithium-inhibited phosphatase BPNT2 in vitro.

Golgi-resident bisphosphate nucleotidase 2 (BPNT2) is a member of a family of magnesium-dependent, lithium-inhibited phosphatases that share a three-dimensional structural motif that directly coordinates metal binding to effect phosphate hydrolysis. BPNT2 catalyzes the breakdown of 3'-phosphoadenosine-5'-phosphate, a by-product of glycosaminoglycan (GAG) sulfation. KO of BPNT2 in mice leads to skeletal abnormalities because of impaired GAG sulfation, especially chondroitin-4-sulfation, which is critical for proper extracellular matrix development.