Amotl2, short for angiomotin-like 2, is a member of the motin family of angiostatin-binding proteins. It serves as a scaffold protein that integrates external and internal stimuli to regulate various signaling pathways [1,2,5]. It is involved in pathways such as the Wnt/β -catenin, Hippo, and may be related to the regulation of protein phosphatase 2A (PP2A) complex-associated signaling [3,4,6]. Amotl2 plays a crucial role in many cellular processes including cell differentiation, migration, angiogenesis, and contact inhibition, and thus is important for normal biological development and disease-related processes [1,4]. Genetic models, like knockout (KO) or conditional knockout (CKO) mouse models, can be valuable tools to study its function.

In glioma, AMOTL2-knockdown promotes the proliferation, migration, and invasion of glioma cells by regulating β-catenin nuclear localization. High AMOTL2 expression in glioma patients is associated with a higher survival rate [3]. In non-small cell lung cancer cells, upregulation of AMOTL2 leads to cell proliferation delay as it inhibits JUN Thr239 dephosphorylation by binding PPP2R2A [6]. In airway smooth muscle cells, AMOTL2 restrains TGF-β1-induced proliferation and extracellular matrix deposition via down-regulation of YAP1 activation [7]. The endothelial deficit of AmotL2 in mice fed a normal diet provokes a pro-inflammatory response and abdominal aortic aneurysms (AAAs), and in human AAA samples, there is a negative correlation between AmotL2 and aortic intima inflammation [8]. The circadian gene ARNTL2 promotes nasopharyngeal carcinoma invasiveness and metastasis through suppressing the AMOTL2-LATS-YAP pathway [9]. In luminal breast cancer, MAGI1 acts as a tumor-suppressor by inhibiting an AMOTL2/p38 stress pathway [10].

In conclusion, AmotL2 is a significant regulator in multiple biological processes. Through model-based research, its role in diseases such as glioma, non-small cell lung cancer, airway-related conditions, aortic diseases, nasopharyngeal carcinoma, and luminal breast cancer has been revealed. These findings enhance our understanding of disease mechanisms and may provide potential therapeutic targets.