Tnnt2, encoding cardiac muscle troponin T, is a key player in the calcium regulation of actin thin filament function, essential for cardiac muscle contraction [2]. It is involved in pathways related to cardiomyocyte contraction and has significant biological importance in heart function. Genetic models, such as those using human induced pluripotent stem cell models, are valuable for studying Tnnt2.

Pathogenic Tnnt2 variants can cause hypertrophic and dilated cardiomyopathies. Hypertrophic cardiomyopathy-associated Tnnt2 variants increase cardiac microtissue contraction, while dilated cardiomyopathy-associated variants decrease it, both paralleling changes in myofilament calcium affinity. Tnnt2 variant-dependent changes in sarcomere contractile function induce graded regulation of 101 gene transcripts, including MAPK signaling targets, HOPX, and NPPB. Based on NPPB reporter activity and cardiac microtissue contraction, some Tnnt2 variants' pathogenicity classification could be re-evaluated [1]. In colorectal cancer, Tnnt2 may act as an oncogene, promoting cell proliferation, invasion, and metastasis through the EGFR/HER2/EMT signal axis. Its overexpression is associated with inferior prognosis, and it may be a potential biomarker and therapeutic target [3,4].

In conclusion, Tnnt2 is crucial for cardiac muscle contraction. Model-based research has revealed its role in cardiomyopathies and colorectal cancer. Understanding Tnnt2 through these models helps in improving heart failure risk determination, treatment efficacy, and provides new insights into disease pathogenesis, especially in the context of cardiomyopathies and colorectal cancer.