Micall2, also known as Molecule interacting with CasL-like protein 2, is believed to regulate cytoskeleton dynamics, tight junction formation, and neurite outgrowth. It is involved in multiple signaling pathways, such as the Wnt/β -catenin signaling pathway [2,3]. Micall2 has significance in various biological processes and diseases, with its abnormal expression often associated with cancer malignancy and disease progression [1-5].

In clear cell renal cell carcinoma (ccRCC), Micall2 was highly expressed in cancer tissues and cell lines compared to paracancerous tissues and normal cells. Upregulated Micall2 promoted ccRCC cell proliferation, migration, and invasion, while gene silencing had the opposite effect, indicating its role in ccRCC malignancy [1].

In colorectal cancer, MICALL2 levels were up-regulated, and it enhanced cell growth and migration via the Wnt/β -catenin pathway. Ubiquitin E3 ligase TRIM21 mediated its ubiquitination and degradation, negatively regulating its tumorigenic activity [2].

In pulmonary fibrosis, MICALL2 was upregulated in bleomycin-induced mice and TGF-β1-stimulated alveolar epithelial type II cells. MICALL2-deficient mice had reduced fibrogenesis and restrained epithelial-mesenchymal transition (EMT), and knockdown of MICALL2 impeded β-catenin nuclear translocation to restrain the EMT process in vitro [3].

In conclusion, Micall2 is involved in regulating cytoskeleton-related functions and multiple signaling pathways. Its abnormal expression contributes to the malignancy of cancers like ccRCC and colorectal cancer, and its role in pulmonary fibrosis development is also significant. The use of gene knockdown or knockout models in these studies has helped to clearly define Micall2's role in these disease conditions, providing potential therapeutic targets for these diseases.