Klhl21, Kelch-like protein 21, is involved in multiple biological functions. It plays roles in cell motility, as the CRL3(KLHL21) E3 ubiquitin ligase promotes cell migration by regulating microtubule and focal adhesion dynamics [3]. It also has a part in cell cycle regulation, being required for cytokinesis and regulating the translocation of the chromosomal passenger complex in anaphase [5]. Additionally, it is associated with signaling pathways such as negatively regulating the NF-κB signaling pathway by targeting IκB kinase-β [4]. Genetic models like knockout (KO) or conditional knockout (CKO) mouse models are valuable for studying Klhl21.

In gastric cancer, genetic deletion of Klhl21 in mice enhances the rapid proliferation of Mist1+ cells and their descendant cells. Klhl21 loss during metaplasia facilitates the recruitment of damaged cells into the cell cycle via STAT3 signaling, and increased STAT3 activity boosts self-renewal and tumourigenicity [1]. In bladder cancer, KLHL21 over-expression in vitro significantly reduces the proliferation, migration and invasion in BC cells, while KLHL21 knockdown accelerates these properties. Animal studies confirm its anti-tumor function in xenograft mouse models [2].

In conclusion, Klhl21 is crucial in regulating cell motility, cell cycle and signaling pathways. The study of Klhl21 using KO/CKO mouse models has revealed its significant roles in gastric and bladder cancer, highlighting its potential as a therapeutic target in these disease areas.