OVOL2: an epithelial lineage determiner with emerging roles in energy homeostasis

Ovo like zinc finger 2 (OVOL2) is an evolutionarily conserved regulator of epithelial lineage determination and differentiation during embryogenesis. OVOL2 binds to DNA using zinc-finger domains to suppress epithelial-mesenchymal transition (EMT), which is critical for tumor metastasis. However, recent studies have suggested some noncanonical roles of OVOL2 that do not rely on the DNA binding of zinc-finger domains or regulation of EMT. OVOL2 and EMT regulators have emerging roles in adipogenesis, thermogenesis, and lipid metabolism. Here, we review different roles of OVOL2 from embryo development to adult tissue homeostasis, and discuss how OVOL2 and other EMT regulators orchestrate a regulatory network to control energy homeostasis. Last, we propose potential applications of targeting OVOL2 to reduce human obesity.