Protein phosphatase 1 regulatory subunit 1B (PPP1R1B)

Protein phosphatase 1 regulatory subunit 1B (PPP1R1B), also known as dopamine- and cAMP-regulated neuronal phosphoprotein (DARPP-32), is a key intracellular signaling protein highly expressed in dopaminoceptive neurons, particularly the striatum. Phosphorylation of DARPP-32 by protein kinase A (PKA) converts it into a potent inhibitor of protein phosphatase 1 (PP1), playing a central role in modulating the response to dopamine and glutamate signaling, synaptic plasticity, and neuronal gene expression. Alternative splicing generates isoforms such as t-DARPP, implicated in multiple cancers where it contributes to drug resistance and enhanced cell survival pathways, notably by activating AKT signaling. In the nervous system, dysregulation of DARPP-32 is linked to neurologic and psychiatric disorders. No direct small-molecule inhibitors of PPP1R1B are used clinically, but its regulatory role makes it an important therapeutic and diagnostic target in both neuroscience and oncology.

Other names

Dopamine- and cAMP-regulated neuronal phosphoproteinDARPP-32DARPP32t-DARPP (truncated isoform)Dopamine and cAMP regulated phosphoproteinFLJ20940

Inhibition of protein phosphatase 1 (via PKA-mediated phosphorylation in neurons); Modulation of downstream kinases (AKT, ERK, mTORC1) in cancer and neuronal cells; Modulation of dopamine and cAMP pathways in neurons.