Igf2, insulin-like growth factor 2, is a paternally expressed growth-promoting gene. It plays a crucial role in the regulation of human embryonic growth and development, as well as in adults' physiology. IGF2 functions through interacting with the IGF1R and is involved in multiple signaling pathways, such as the PI3K-AKT and Hippo-YAP1 pathways, and has pleiotropic tissue-specific and developmental-stage-dependent actions [1,3].

In animal and human studies, IGF2 has been shown to be essential in various biological processes. For instance, in colorectal cancer, CAF-derived IGF2 promotes tumor growth, migration, and invasion via the IGF2-IGF1R-YAP1 axis [3]. Mutations in IGF2 can lead to Silver-Russell syndrome (SRS), with distinct phenotypic features compared to H19/IGF2:IG-DMR epimutations [2]. Also, IGF2 is overexpressed in adrenocortical carcinoma, influencing cell proliferation, metabolism, and viability [4]. In the central nervous system, alterations in IGF2 are associated with psychiatric and neurological disorders [5]. In the context of pulmonary diseases, IGF2 has a dual impact on alveolar stem cell function during tobacco-induced injury repair, being involved in the development of pulmonary emphysema and cancer [6].

In conclusion, Igf2 is of great biological significance in growth regulation, especially during development, and is associated with multiple disease conditions including cancer, imprinted disorders, and neurological/psychiatric diseases. The study of Igf2 using gene knockout and other genetic models has been instrumental in understanding its role in these biological processes and diseases [1-3,5,7,9].