Hhex, short for Hematopoietically expressed homeobox, is a transcription factor crucial for the development of multiple lymphoid lineages, hematopoietic stem cell self-renewal, and emergency hematopoiesis [6]. It also plays a role in embryonic development and is involved in various biological processes such as hepatogenesis [4].

In disease-related research, in hepatocellular carcinoma (HCC), HHEX is overexpressed, promoting cell proliferation, migration, invasion, and stem-cell-like properties through the ABI2/SLC17A9 axis [1]. In myeloid neoplasms, HHEX cooperates with mutant ASXL1 to enhance the proliferation of hematopoietic stem and progenitor cells (HSPCs) by inhibiting apoptosis and blocking differentiation [5]. In thyroid cancer, HHEX acts as a tumor suppressor, and its low expression is associated with enhanced cell proliferation, migration, and invasion [3]. Additionally, certain HHEX gene polymorphisms are associated with an increased risk of gestational diabetes mellitus [2].

In conclusion, Hhex has diverse functions in normal development and disease. Gene knockout and other genetic models have revealed its roles in promoting cancer development in HCC, myeloid neoplasms, and as a suppressor in thyroid cancer. The discovery of its association with gestational diabetes mellitus through genetic polymorphism analysis also emphasizes its significance in disease-related genetics.