Novel Insights into TSC22D Family Genes in Metabolic Diseases and Cancer

Transforming growth factor-beta 1 (TGF-β1)-stimulated clone 22 domain (TSC22D) family genes (including <i>TSC22D1-TSC22D4</i>) were identified as transcription factors. It has been demonstrated that they display multiple functions due to proteins' isoforms, redundancy, and other factors. Formerly, researchers mainly focused on its functions, like controlling cell growth and development, cell apoptosis, and balance of osmotic pressure in vivo. Nowadays, growing evidence indicates that they also play an important role in metabolic regulation and the immune system and are expected to be a new potential target for the treatment of diabetes or obesity. Despite this, it has been shown that TSC22D family genes have an inhibitory effect in multiple tumors. In this review, we significantly synthesized advances in metabolism, showing that <i>TSC22D3</i> could control lipid accumulation via modulating adipogenesis and adipose differentiation, while <i>TSC22D4</i> could regulate insulin sensitivity and gluconeogenesis by affecting Akt (serine/threonine kinase, also known as protein kinase B, or PKB) phosphorylation. Moreover, we provide novel insights, including the fact that TSC22D family genes function as a double-edged sword in cancer due to the type of tumor and tumor microenvironment (TME).