GNB1L, encoding a G-protein beta-subunit-like polypeptide, is located in the critical region for DiGeorge syndrome on 22q11 [3]. It is a key regulator of the DNA damage response (DDR) signaling pathway, acting as a co-chaperone specifically regulating phosphatidylinositol 3-kinase-related kinases (PIKKs) such as ATR, which is crucial for maintaining genome stability [1,2].

In terms of disease associations, GNB1L has been linked to multiple psychiatric disorders. In Chinese Han populations, it shows an association with bipolar disorder and schizophrenia but not with major depressive disorder [5]. There is also evidence for its involvement in autism, as missense variants in conserved residues of GNB1L were found in families with autism [6]. Additionally, in mouse models, hemizygous deletion of Gnb1l can cause deficits in pre-pulse inhibition, a sensory-motor gating defect associated with schizophrenia, and in human studies, markers associated with psychosis are correlated with alterations in GNB1L expression [7]. Also, GNB1L expression is lower in postmortem prefrontal cortex of patients with schizophrenia compared to controls, and haloperidol treatment increased Gnb1l gene expression in mouse prefrontal cortex [8]. In chickens, a 31-bp indel in the 5' UTR region of GNB1L significantly affects body weight and carcass traits, which may serve as a candidate molecular marker for chicken genetics and breeding [4].

In conclusion, GNB1L plays essential roles in DDR signaling and is associated with multiple psychiatric disorders. Mouse models, especially those with Gnb1l hemizygous deletion, have been crucial in revealing its role in schizophrenia-related phenotypes. Its association with chicken growth traits also showcases its diverse functions across species, highlighting the importance of GNB1L in both biological processes and disease-related research.