Guanine nucleotide dissociation inhibitor (GDI) which functions as a receptor-independent activator of heterotrimeric G-protein signaling. Keeps G(i/o) alpha subunit in its GDP-bound form thus uncoupling heterotrimeric G-proteins signaling from G protein-coupled receptors. Controls spindle orientation and asymmetric cell fate of cerebral cortical progenitors. May also be involved in macroautophagy in intestinal cells. May play a role in drug addiction. Interacts with INSC/inscuteable and FRMPD1 (By similarity). Interacts with GNAI1, GNAI2 and GNAI3 preferentially in their GDP-bound state. May also interact with GNAO1. Interacts with STK11/LKB1 and MACF1. Isoform 2 is not associated with membranes. Isoform 4 is specifically expressed in brain by neurons and also detected in testis, liver, kidney, heart and pancreas (at protein level). Highly expressed in cerebellum and subventricular zone-olfactory bulb system. Isoform 2 and isoform 3 are specifically expressed in heart and are also detected in brain. Expression reaches a maximum at postnatal day 7 before to significantly decrease. Up-regulated in prefrontal cortex and core region of nucleus accumbens during late withdrawal from chronic cocaine administration. The GoLoco domains mediate interaction with G(i/o) alpha. The GoLoco domains are essential for the GDI activity toward G(i/o) alpha. Phosphorylation regulates interaction with G(i/o) alpha. Responsible for altered neurotransmission and altered behavior like drug seeking associated with cocaine addiction. Depletion in prefrontal cortex reverses the behavioral consequences of cocaine addiction while overexpression in drug-naive animals induces addictive behavior upon acute cocaine injection. Produced by initiation at Met-62 of isoform 3. Mutagenesis of Met-1 into Gly prevents expression of this isoform. Combined mutagenesis of Gln-57, Gln-105 and Gln-129 into Ala alters the function of the GoLoco domains. Minor isoform. Mutagenesis of Met-1 into Gly leads to expression of isoform 2. Produced by alternative splicing. Belongs to the GPSM family.