Hint1, short for Histidine Triad Nucleotide-Binding Protein 1, is a nucleoside phosphoramidase. It is involved in regulating transcription, cell-cycle control, and has both enzymatic and non-enzymatic activity. Hint1 is widely expressed in almost every organ and participates in multiple biological processes, and its dysfunction is associated with various diseases [2,4].

In cardiac hypertrophy research, Hint1-deficient mice showed deteriorated cardiac hypertrophy after transverse aortic constriction, while cardiac-specific overexpression of Hint1 alleviated it. Hint1 was found to attenuate cardiac hypertrophy by suppressing HOXA5 expression through inhibiting PKCβ1 membrane translocation and phosphorylation, thus affecting the MEK/ERK/YY1 signal pathway [1]. In addition, in aged Hint1 knockout (KO) mice, they showed reduced anxiety-like and depression-like behaviors and enhanced cognitive performance compared to age-matched wild-type mice, indicating that Hint1 deficiency can counteract age-related emotion and cognition dysfunction [3].

In conclusion, Hint1 plays a crucial role in biological processes related to cardiac function and neuropsychiatric functions. The use of Hint1 KO mouse models has revealed its protective role in cardiac hypertrophy and its impact on age-related emotional and cognitive functions, providing potential targets for the treatment of related diseases.