[5][9] DARPP-32 is critical for dopamine dependent striatal synaptic plasticity,[12] possibly by serving as a dopamine-dependent gating mechanism for calcium/CaMKII signaling.

As such PPP1R1B affects dopamine,[14] glutamate and adenosine; and there is some support for a role of the gene in schizophrenia, as well as being involved in the action of drugs including cocaine, amphetamine, nicotine, LSD, caffeine, PCP, ethanol and morphine,[15] and in Parkinson's disease or EPS (Extra-pyramidal symptoms).

[20][21] A considerable proportion of the psychomotor effects of cannabinoids can be accounted for by a signaling cascade in striatal projection neurons involving PKA-dependent phosphorylation of DARPP-32, achieved via modulation of dopamine D2 and adenosine A2A transmission.

[24] Both isoforms are overexpressed in a number of cancers including those derived from gastric, colon, prostate, esophageal, breast, and lung tissues.

[25][26] In Her-2-positive breast cancer cells, t-Darpp overexpression imparts resistance to Trastuzumab (Herceptin), the chemotherapy drug that shuts down the Her-2 signaling pathway.