Trp53inp1, also known as tumor protein 53-induced nuclear protein 1, is a stress-induced protein involved in multiple biological functions. It acts as a dual positive regulator of transcription and autophagy, and is part of pathways like the Trp53-Trp53inp1-Tnfrsf10b pathway. It is crucial in the cell stress response, playing a role in processes such as DNA damage response, apoptosis regulation, and maintaining neuronal homeostasis [1,2]. Genetic models, especially knockout (KO) mouse models, have been instrumental in studying its functions.

In Trp53inp1-deficient mice, several phenotypes were observed. In the context of spermatogonial stem cells (SSCs), Trp53inp1 is part of the Trp53-Trp53inp1-Tnfrsf10b pathway regulating radiation-induced SSC apoptosis; Trp53inp1 deficiency increased SSC survival after irradiation [1]. In the nervous system, Trp53inp1 -/- mice showed additional loss of dopamine neurons in the substantia nigra during ageing and in a Parkinson's disease model [2]. In the digestive system, Trp53inp1-deficient mice had an increased incidence and multiplicity of colorectal tumors and more severe DSS-induced acute colitis, with higher oxidative load [3].

In conclusion, Trp53inp1 is essential in regulating apoptosis, maintaining neuronal homeostasis, and controlling oxidative stress. The Trp53inp1 KO mouse models have significantly contributed to understanding its role in diseases such as Parkinson's disease and colorectal cancer, highlighting its potential as a therapeutic target in these disease areas.