Gli2, a zinc-finger transcription factor, is a key component of the Sonic Hedgehog (Shh) signaling pathway [2,3]. This pathway is crucial in multiple biological processes such as embryonic development, cell differentiation, and tissue homeostasis. Genetic models, especially knockout (KO) mouse models, have been instrumental in understanding Gli2's functions.

Gli2 mutant mice display hypoplastic anterior and absent posterior pituitary glands, highlighting its role in pituitary development [2]. In the context of tumorigenesis, Gli2-mediated inflammation in the tumor microenvironment (TME) has been identified. It can modulate cytokine genes in the TME, playing a role in cancer development and progression independent of Hedgehog (HH) stimulation [1]. In chronic kidney disease, the Shh-Gli2-Runx2 axis inhibits vascular calcification, with Gli2 promoting the ubiquitin-proteasomal degradation of Runx2 [4]. In colorectal cancer, the suppressive GLI2 fragment enhanced by linoleic acid (LA) can increase tumor cell stemness and liver metastasis [5]. In pancreatic cancer cells, the association between CEP164 and GLI2 controls Hh signaling, even in the absence of primary cilia [6]. In thalamocortical projection development, Gli2-mediated Shh signaling is required for correct axon guidance, as Gli2 knockout embryos show misdirected thalamocortical axons [7]. In hepatocellular carcinoma, TGF-β1/SMAD3-driven GLI2 isoform expression contributes to aggressive phenotypes [8].

In conclusion, Gli2 is essential for normal development and homeostasis, with its disruption leading to various diseases. The study of Gli2 KO mouse models has provided significant insights into its functions in pituitary development, cancer, vascular calcification, and neural development. Understanding Gli2's roles may offer potential therapeutic targets for related diseases.