Prr14, or Proline Rich 14, is a protein that plays a crucial role in organizing H3K9me3-modified heterochromatin at the nuclear lamina [1,4,7]. It dynamically associates with both the nuclear lamina and heterochromatin, and its two HP1-binding sites contribute to this association [1]. It also seems to be involved in multiple signaling pathways, such as the PI3K/Akt/mTOR pathway, which are important in various biological processes and disease-related events [2,5,6,8].

Specific knockout (KO) of skeletal muscle Prr14 in mice led to muscle atrophy. This demonstrated that Prr14 is crucial for mediating mechanotransduction, regulating MEF2C's activity, and maintaining myofiber identity [3]. In cancer research, RNA interfering (RNAi)-mediated inhibition of Prr14 in cutaneous squamous cell carcinoma (cSCC) cells suppressed cell proliferation, migration, and invasion while promoting apoptosis, suggesting its role as an oncogene in cSCC through the PI3K/Akt/mTOR signal pathway [2]. Similarly, in colon cancer, down-regulation of Prr14 inhibited cell growth, migration, invasion, and the epithelial-mesenchymal transition (EMT) process [5]. In breast cancer, Prr14 overexpression promoted cell proliferation and tumor formation by activating the PI3-kinase/Akt/mTOR pathway and inhibiting the CHEK2 pathway [6].

In conclusion, Prr14 is essential for the organization of heterochromatin at the nuclear lamina. Through gene-knockout models, its significance in skeletal muscle function and as an oncogene in multiple cancer types has been revealed. These findings offer new therapeutic avenues for skeletal muscle pathologies and cancer treatment.