Lats2, short for large tumor suppressor kinase 2, is a core kinase of the Hippo pathway. The Hippo pathway is evolutionarily conserved and regulates numerous biological processes like cell growth, fate decision, organ size control, and regeneration [1]. Lats2 is crucial in maintaining cellular homeostasis and its dysregulation is associated with various diseases. Genetic models, such as knockout (KO) or conditional knockout (CKO) mouse models, have been instrumental in studying its functions.

In endothelial cell-specific Lats2 KO mice, myofibroblast formation, extensive fibrosis, and osteosclerosis occur, impairing bone marrow function, which reveals Lats2 as a suppressor of bone marrow fibrosis [2]. In proximal tubular Lats2-CKO mice, more severe tubular maladaptive repair, inflammatory infiltration, interstitial fibrosis, and apoptosis are seen following acute kidney injury, suggesting Lats2 deficiency aggravates ischemia/reperfusion injury-induced maladaptive repair via the tubular MDM2-p53 axis [3]. Systemic Lats2+/- mice show attenuated cardiac hypertrophy, dysfunction, interstitial fibrosis, and apoptosis induced by transverse aortic constriction, indicating Lats2 promotes heart failure by stimulating p53-mediated apoptosis during pressure overload [4].

In conclusion, Lats2 plays essential roles in multiple biological processes through its involvement in the Hippo pathway. Model-based research, especially using Lats2 KO/CKO mouse models, has provided valuable insights into its functions in diseases such as bone marrow fibrosis, kidney injury-related maladaptive repair, and heart failure. Understanding Lats2 may offer potential strategies for treating these diseases.