Thrap3, also known as thyroid hormone receptor-associated protein 3, is involved in multiple biological processes and associated pathways. It has been shown to participate in transcriptional regulation, interacting with key proteins in various signaling cascades, which is of great biological importance. Gene knockout models, especially KO/CKO mouse models, have been crucial in uncovering its functions [1-10].

In a high-fat diet-induced NAFLD model, liver-specific Thrap3 knockout improved lipid accumulation and metabolic properties, enhanced autophagy and mitochondrial function. It achieved this by increasing the cytosolic translocation and activation of AMPK [1]. In osteogenesis, Thrap3 promoted osteoblast differentiation through the Thrap3-Sox9-Runx2 axis by inhibiting the degradation of Runx2 [2]. In cancer cells, loss of Thrap3 increased R-loop accumulation and DNA damage, indicating its role in R-loop resolution [3]. THRAP3 depletion in 3T3-L1 adipocytes increased lipolysis and pro-inflammatory gene expression, and reduced the mRNA and protein levels of PPARγ [4].

In conclusion, Thrap3 is involved in diverse biological functions such as lipid metabolism, osteogenesis, R-loop regulation, and adipocyte function. The Thrap3 KO/CKO mouse models have significantly contributed to understanding its role in diseases like NAFLD, osteoporosis, and potentially in cancer and diabetes-related adipocyte dysfunctions, providing insights for potential therapeutic strategies.