GNAI2, also referred to as the proto - oncogene gip2, encodes the α - subunit of G - protein i2. It is a signaling modulator or transducer involved in several transmembrane signaling systems, playing crucial roles in multiple biological processes. It participates in the melanogenesis signaling pathway, and is also associated with pathways like Hippo/YAP, PI3K/AKT, and may interact with toll - like receptor 4 signaling in the context of NASH [1,2,4,6].

In rabbit melanocytes, overexpression of GNAI2 promotes melanocyte proliferation, inhibits apoptosis, and increases melanin content, while knockdown has the opposite effect [1]. In ovarian cancer, silencing GNAI2/gip2 in SKOV3 cells led to changes in the expression of 264 genes, with functional annotation indicating its role in stimulating oncogenic/growth - promoting genes [3]. In gastric cancer, high GNAI2 expression was associated with poor prognosis, and it activated the PI3K/AKT pathway to promote cell growth and migration [4]. In NASH, hepatocyte - specific Gnai2 - deficient mice had reduced steatohepatitis, suppressed inflammation markers, and increased lipophagy compared to control mice, suggesting GNAI2 exacerbates NASH progression [6]. In colitis - associated tumorigenesis, GNAI1 and GNAI3 reduce tumorigenesis by down - regulating GNAI2 expression, and in mice with disrupted Gnai1 and Gnai3, increased GNAI2 levels were associated with more severe colitis and increased tumor development [5].

In conclusion, GNAI2 is a key regulator in various biological processes and disease conditions. Gene knockout or knockdown models in different organisms and cell lines have revealed its role in cell proliferation, apoptosis, melanogenesis, and in diseases such as ovarian cancer, gastric cancer, NASH, and colitis - associated tumorigenesis. Understanding GNAI2 function through these models provides insights into potential therapeutic targets for related diseases.