Thrap3, also known as thyroid hormone receptor-associated protein 3, is involved in multiple biological processes. It participates in regulating autophagy, osteogenesis, R-loop resolution, adipocyte function, and is associated with signaling pathways such as the AMPK, Sox9-Runx2, and CLK1-PPARγ axes. Its study using gene knockout models helps to understand its functions and roles in related diseases [1-4, 10].

In a high-fat diet-induced nonalcoholic fatty liver disease (NAFLD) model, liver-specific Thrap3 knockout improved lipid accumulation and metabolic properties, enhanced autophagy and mitochondrial function, and increased the cytosolic translocation and activation of AMPK, indicating Thrap3 promotes NAFLD progression by suppressing AMPK-mediated autophagy [1]. In osteoblast differentiation, Thrap3 promotes osteogenesis through the Thrap3-Sox9-Runx2 axis by inhibiting the degradation of Runx2 [2]. In cancer cells, Thrap3 promotes R-loop resolution via interaction with methylated DDX5, and its loss increases R-loop accumulation and DNA damage [3]. In 3T3-L1 adipocytes, THRAP3 depletion reduces PPARγ mRNA levels, increases pro-inflammatory response, and attenuates TZD-mediated anti-inflammatory effects [4].

In conclusion, Thrap3 is essential in various biological processes including autophagy, osteogenesis, R-loop regulation, and adipocyte function. Gene knockout studies of Thrap3 have revealed its significant roles in diseases like NAFLD, osteoporosis, and potentially cancer, providing potential therapeutic targets for these diseases.