Prkg1, encoding cGMP-dependent protein kinase type I, is a key molecule in the cGMP signaling pathway. It is involved in multiple biological processes, with its functions including regulating cell-related activities such as contraction in aortic smooth muscle cells, and its role in pathways like NO/cGMP/PKG is crucial for various physiological functions [3,5].

In mice, genetic deletion of Prkg1 led to a greater vulnerability to and less recovery from noise-induced hearing loss (NIHL), suggesting an endogenous protective cGMP-Prkg1 signaling pathway in cochlear hair cells and hearing function [4].

In the dorsomedial hypothalamus (DMH) of mice, within DMHPpp1r17 neurons, Prkg1-regulated phosphorylation and translocation of Ppp1r17 affect gene expression regulating synaptic function, and DMH-specific Prkg1 knockdown can ameliorate age-associated dysfunction in white adipose tissue (WAT), increase physical activity, and extend lifespan [2]. Also, vericiguat, used to treat heart failure, can up-regulate Prkg1, which in turn activates PINK1 and inhibits the STING/IRF3 pathway, thus alleviating doxorubicin-induced cardiotoxicity in mice [1].

In conclusion, Prkg1 is essential in the cGMP signaling pathway and plays important roles in various biological processes and disease conditions. Studies using Prkg1-related genetic mouse models have revealed its significance in NIHL, aging-related processes, and cardiotoxicity, providing insights into the underlying molecular mechanisms and potential therapeutic targets.