GRIK3, also known as Glutamate ionotropic receptor kainate type subunit 3, is a key excitatory neurotransmitter receptor in the mammalian brain. It belongs to the glutamate kainate receptor family and mainly participates in the neuroactive ligand receptor interaction pathway [3]. GRIK3 is involved in normal neurophysiologic processes such as synaptic potentiation, which is crucial for learning and memory [2].

GRIK3 has been implicated in multiple disease conditions. In non-small cell lung cancer (NSCLC), GRIK3 deficiency promotes cancer progression. It increases the expression of UBE2C and CDK1, activating the Wnt signaling pathway [1]. In gastric cancer (GC), higher GRIK3 expression is associated with poor survival outcomes, and it may be an independent prognostic factor [3]. In breast cancer, GRIK3 promotes epithelial-mesenchymal transition by regulating SPDEF/CDH1 signaling [4]. In colorectal cancer, the circRNA hsa_circ_0038646 promotes cell proliferation and migration via miR-331-3p/GRIK3, and circASXL1 acts oncogenically in CRC via sponging miR-1205 to upregulate GRIK3 [5,7]. Also, CHRNA3, GABRD, GRIK3, and GRIK5 were identified as a neurotransmitter receptor-related prognostic genes signature in colorectal cancer [9]. A girl with a 2.6-Mb microdeletion in 1p34.3 involving GRIK3 presented with severe developmental delay, suggesting GRIK3 haploinsufficiency may be responsible [2]. However, studies on GRIK3 (T928G) gene variants in schizophrenia patients and their relatives showed no significant differences in genotype distributions between patients and relatives, though the GG genotype frequency was higher in patients than in healthy controls [6]. And a family-based and case-control study found that the GRIK3 Ser310Ala polymorphism is not associated with alcohol dependence [8].

In conclusion, GRIK3 is essential for normal neurophysiological functions. Its dysregulation is associated with multiple cancers and developmental delay. Studies on GRIK3, including those potentially using gene knockout or conditional knockout models in the context of these diseases, help us understand its role in disease pathogenesis, providing potential directions for diagnosis, prognosis, and treatment development.