Llgl2, lethal (2) giant larvae protein homolog 2, is a scaffolding protein that belongs to the Lgl family. It is involved in regulating epithelial cell apicobasal polarity, asymmetric cell division, cell migration, and progenitor cells self-renewal [1,3]. It has been shown to interact with various proteins and pathways, playing a crucial role in multiple biological processes. Genetic models, especially KO/CKO mouse models, can be valuable for further exploring its functions.

In ovarian cancer, overexpression and knockdown experiments of LLGL2 demonstrated that it inhibited the migration and invasion of ovarian cancer cells in vitro and reduced metastatic implant foci in vivo. Mechanistically, LLGL2 regulated cytoskeletal remodeling by interacting with ACTN1 [1]. In ER + breast cancer, LLGL2 was overexpressed and promoted cell proliferation under nutrient stress by regulating leucine uptake through forming a trimeric complex with SLC7A5 and YKT6 [2]. In hepatocellular carcinoma (HCC), LLGL2 was up-regulated, and its high expression predicted poor prognosis. LLGL2 promoted HCC cells proliferation, migration, and invasion through the PI3K/ATK signaling pathway by promoting calcium ion influx [3]. In endometrial cancer, LLGL2 was upregulated, promoted cell proliferation, migration, and invasion, and might promote the transduction of the Hedgehog signaling pathway [5]. In prostate-related diseases, in BPH-1 cells, LLGL2 was involved in cell proliferation by regulating autophagosome formation, and in prostate cancer, LLGL2 knockdown induced autophagy flux, inhibited epithelial-mesenchymal transition (EMT), and reduced tumor size in a xenograft mouse model [4,6].

In conclusion, Llgl2 plays diverse and significant roles in various biological processes and diseases. Model-based research, especially KO/CKO mouse models, has revealed its functions in cancer metastasis, cell proliferation under nutrient stress, and regulation of signaling pathways and autophagy. Understanding Llgl2 is crucial for elucidating disease mechanisms and developing potential therapeutic strategies in cancer and prostate-related diseases.