Tra2b, also known as SFRS10, is an RNA binding protein that plays well-established roles in developmentally regulated alternative splicing, especially during Drosophila sexual differentiation. In mammals, it is essential for embryogenesis. Precise regulation of alternative splicing by Tra2b is critical to the development and function of the central nervous system [2].

In murine cortical neurogenesis, TRA2B depletion in cortex-specific Tra2b mutant mice (a form of in vivo KO model) results in apoptosis of neural progenitor cells and disorganization of the cortical plate, indicating its essential role in proper cerebral cortex development [2]. In T-cell fate regulation, an evolutionarily ultraconserved poison exon (PE) in Tra2β undergoes autoregulated splicing in response to antigen-receptor stimulation, which is crucial for TCR-induced effector T cell expansion, function, and survival [3]. In endometrial carcinoma, overexpression of TRA2B promotes cell viability, proliferation, invasion, and inhibits apoptosis, while siRNA-TRA2B treatment has the opposite effects, suggesting its role in the pathogenesis of endometrial carcinoma [1]. Also, predicted loss-of-function variants in the 5' portion of TRA2B in humans cause a new neurodevelopmental syndrome through a dominant-negative mechanism involving alternative translation start site usage and overexpression of a shorter Tra2β protein [4].

In conclusion, Tra2b is essential for multiple biological processes such as neural development, T-cell fate determination, and is involved in diseases like endometrial carcinoma and a novel neurodevelopmental syndrome. The use of KO/CKO mouse models and functional studies in human cells have significantly contributed to understanding Tra2b's functions and its implications in disease, highlighting its importance as a potential therapeutic target in related disease areas.