Pex5, the peroxisomal matrix protein import receptor, is crucial for peroxisome biogenesis. It recognizes peroxisomal matrix proteins in the cytosol and transports them to the peroxisomal lumen, a process fundamental to peroxisome function [1]. Peroxisomes are essential organelles, and their dysfunction can lead to various diseases. Genetic models, such as knockout (KO) mouse models, are valuable tools for studying Pex5.

In male mice, pre-meiotic deletion of Pex5 using Stra8-Cre mice crossed with Pex5flox/flox mice led to spermatogenesis failure and infertility. Loss of Pex5 in spermatocytes caused multinucleated giant cell formation, meiotic arrest, abnormal tubulin expression, and deformed acrosome formation. Impaired peroxisome function due to Pex5 deletion induced reactive oxygen species (ROS) redundancy, increasing germ cell apoptosis and decreasing autophagy [4]. In cardiomyocytes, down-regulation of Pex5 was observed in Sirt3-deficient mice and angiotensin II-induced cardiac hypertrophic mice. Pex5 knockdown abolished the protective effect of SIRT3 against cardiomyocyte hypertrophy, while overexpression alleviated the hypertrophic response [2]. Additionally, in primary neonatal rat cardiomyocytes, Pex5 protein expression declined upon treatment with phenylephrine. Overexpression of Pex5 alleviated cardiomyocyte hypertrophy, improved redox imbalance, and suppressed activation of redox-sensitive signaling pathways like mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3) [3].

In conclusion, Pex5 is essential for maintaining normal physiological functions in spermatogenesis and cardiomyocytes. Through gene knockout models in mice, we have learned that Pex5 plays a key role in preventing spermatogenesis failure and cardiomyocyte hypertrophy by regulating ROS levels and related signaling pathways. These findings contribute to our understanding of diseases related to peroxisome dysfunction in the context of male infertility and heart diseases.