The emerging roles of ITM2A: At the molecular crossroads of development and pathogenesis
Summary Integral membrane protein 2A (ITM2A) is a type II transmembrane glycoprotein belonging to the BRICHOS superfamily. It primarily regulates organismal development and homeostasis and exhibits tumor-suppressive functions. Its expression is precisely regulated by a multidimensional network involving transcription factors, epigenetic modifications, and environmental signals. Within cellular signaling networks, ITM2A modulates multiple key pathways, including BMP, JAK/STAT, ERK, Hedgehog, and PKA-CREB. ITM2A is essential for the differentiation and functional maturation of various tissues, such as cartilage, bone, and muscle. Dysregulation of ITM2A function or expression is closely associated with malignancies, thyroid disorders, and acute transplant rejection. This review systematically summarizes the complex regulatory mechanisms of ITM2A in growth, development, and disease, with a particular focus on skeletal development and tumorigenesis, aiming to provide a theoretical basis for its potential use as a biomarker for development and disease diagnosis/treatment, as well as for the development of ITM2A-targeted therapeutics.