Tpm3, short for Tropomyosin 3, is one of the tropomyosin genes (TPM1-4) contributing to the functional diversity of skeletal muscle fibers. Since its discovery in 1988, it has been recognized as an essential regulator of muscle contraction in slow muscle fibers [1]. Tropomyosin, including Tpm3, binds to the troponin complex and controls myosin heads' access to actin in a Ca2+-dependent manner, also maintaining thin filament length by regulating tropomodulin and leiomodin [4].

Mutations in Tpm3 have been associated with congenital myopathies, such as cap myopathy [1,8]. In esophageal cancer, Tpm3 promotes cell proliferation, migration, and metastatic potential, and stimulates the epithelial-mesenchymal transition via regulating MMP2/9 expression [2]. In cervical cancer, Tpm3 upregulation is associated with reduced overall survival, and it promotes tumor proliferation and metastasis in vivo and in vitro, while also correlating with intratumoral immune cell infiltration and immune checkpoint activity [6]. Rearrangements of Tpm3 with genes like ALK are involved in rare subtypes of adult renal cell carcinoma [3,5,7], and Tpm3::NTRK1 rearrangement is associated with a rare type of uterine sarcoma [9].

In conclusion, Tpm3 plays crucial roles in muscle function, especially in slow muscle fibers, and is involved in various disease conditions including congenital myopathies, multiple types of cancers. Research on Tpm3 using in vivo and in vitro models has enhanced our understanding of its functions and associated disease mechanisms, which may contribute to developing new diagnostic and treatment strategies for related diseases.