Catalyzes the first reaction in the primary pathway for the renal catabolism of glutamine. Plays a role in maintaining acid-base homeostasis. Regulates the levels of the neurotransmitter glutamate, the main excitatory neurotransmitter in the brain (PubMed:30575854, PubMed:30239721, PubMed:30970188). Lacks catalytic activity. H2O + L-glutamine = L-glutamate + NH4(+) Isoform 1 and isoform 3 are activated by phosphate. Inhibited by BPTES. BPTES binds between subunits and favors dissociation of the tetramer into dimers (PubMed:22049910). Inhibited by 6-diazo-5-oxo-L-norleucine (DON) (PubMed:24451979). Enzyme activity is stimulated by phosphorylation (PubMed:22538822). Homotetramer, dimer of dimers (PubMed:22538822, PubMed:26988803, PubMed:28526749, PubMed:29317493). The tetramers can assemble into rod-like oligomers (in vitro), but the physiological significance of this is not clear (By similarity). Interacts with RAF1 and MAP2K2 (PubMed:22538822). Interacts with ATCAY; the interaction is direct and may control GLS localization, negatively regulating its activity. The 74-kDa cytosolic precursor is translocated into the mitochondria and processed via a 72-kDa intermediate to yield the mature 68- and 65-kDa subunits. Produced by the proteolytic processing of the 74-kDa cytosolic precursor. Produced by the proteolytic processing of the 74-kDa cytosolic precursor. Isoform 1 and isoform 3 are detected in brain cortex. Isoform 3 is highly expressed in astrocytoma, ganglioglioma and ependymoma. Isoform 1 is highly expressed in brain and kidney, but not detected in liver. Isoform 3 is highly expressed in heart and pancreas, detected at lower levels in placenta, lung, pancreas and kidney, but is not detected in liver. Isoform 2 is expressed in cardiac and skeletal muscle. The C-terminal ANK repeats prevent the assembly of the supra-tetrameric filaments. A highly mobile activation loop at the dimer-dimer interface is important for enzyme activity. Synthesized as a 74-kDa cytosolic precursor which is proteolytically processed by the mitochondrial-processing peptidase (MPP) via a 72-kDa intermediate to yield the mature mitochondrial 68- and 65-kDa subunits. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. Belongs to the glutaminase family. Isoform 3 is predicted to be expressed at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. Contrary to expectations, it has been shown to be well expressed, and the encoded protein is detected in mitochondria (PubMed:11015561, PubMed:17940881, PubMed:22228304). Extended N-terminus.