The brain-specific STEP (striatal enriched phosphatase) family of protein tyrosine phosphatases (PTPs) comprises both transmembrane and cytosolic protein members which are the products of alternative splicing. STEP family members are expressed in the dopaminoceptive neurons of the CNS, with highest expression in the basal ganglia and related structures. The STEP protein regulates the N-methyl-d-aspartate receptor (NMDAR) complex; STEP depresses both NMDAR single-channel activity and synaptic currents. The membrane-associated STEP61 isoform localizes in the postsynaptic densities (PSDs) of striatal neurons. STEP61 contains a single tyrosine phosphatase domain, two proline-rich domains and two transmembrane domains. The STEP61 protein associates with the Src family kinase member Fyn when Fyn is phosphorylated at Tyr-420 and not Tyr-431. Upon association, STEP61 dephosphorylates Tyr-420 residue and may thus regulate Fyn activity in PSDs. Isolated from mouse brain, the STEP20 isoform lacks the conserved tyrosine phosphatase domain. The human STEP gene maps to chromosome 11p15.2-p15.1.