Tgm2, also known as transglutaminase 2, is a multifunctional enzyme with transglutaminase crosslinking, G protein signaling and kinase activities. It is involved in various biological processes such as cell adhesion, migration, and differentiation, and is associated with pathways like autophagy, mTOR signaling, and BMP signaling [1,2,6,7]. Its biological importance spans across multiple areas including cancer development, tissue repair, and muscle regeneration. Genetic models, such as knockout (KO) mouse models, are valuable for studying its functions.

In glioblastoma, knocking down Tgm2 inhibits the fusion of autophagosomes with lysosomes, enhancing radiosensitivity [1,4]. In gastric cancer, Tgm2 promotes malignant progression by suppressing the TRIM21-mediated ubiquitination/degradation of STAT1 [2]. In hepatocellular carcinoma, TGM2-mediated histone serotonylation promotes HCC progression via the MYC signalling pathway [3]. In MDCK cells, Tgm2 knockout significantly enhances cell migration, invasion, proliferation, and tumorigenesis in nude mice [5]. In myoblasts, knockdown of Tgm2 suppresses myoblast differentiation, while overexpression promotes it [6]. In ductular reaction during cholestatic liver injury, deletion of Tgm2 affects the functionality and maturity of proliferative cholangiocytes and suppresses BMP-mediated hepatocyte-to-cholangiocyte metaplasia [7].

In conclusion, Tgm2 plays diverse and crucial roles in multiple biological processes and disease conditions. The use of KO/CKO mouse models has significantly contributed to understanding its functions in areas such as cancer, muscle regeneration, and liver injury repair, providing potential therapeutic targets for these diseases.