Ankrd2, also known as Arpp (ankyrin repeat, PEST sequence, and proline-rich region), is a member of the muscle ankyrin repeat protein family. It is mostly expressed in skeletal muscle, where it plays a crucial role in the transcriptional response to stress induced by mechanical stimulation and cellular reactive oxygen species. It is involved in pathways like NF-κB -mediated inflammatory response during muscle differentiation and may link the sarcomere to the nucleus, participating in muscle gene regulation [1,2,3].

In Emery-Dreifuss muscular dystrophy 2, a LMNA-linked disease, mutated lamins change the dynamics of Ankrd2 nuclear import, affecting oxidative stress response [1]. In Ankrd2-knockout or-overexpressing primary myoblasts, Ankrd2 levels inversely correlated with pro-inflammatory gene expression, and it repressed inflammatory responses through interaction with NF-κB repressor subunit p50 [2]. In osteosarcoma, Ankrd2 knockdown impaired the activation of PI3K/Akt and ERK1/2 pathways, reduced cell cycle regulators, and enhanced sensitivity to chemotherapeutic drugs like doxorubicin and cisplatin [4].

In conclusion, Ankrd2 is essential for muscle stress response, regulation of inflammatory responses during muscle differentiation, and has implications in muscle-related diseases like muscular laminopathies. In addition, its role in cancer, specifically osteosarcoma, highlights its potential as a therapeutic target in improving chemotherapeutic efficacy. The study of Ankrd2 using gene knockout models has provided valuable insights into its functions and its involvement in disease conditions [1,2,4].