Ppif, also known as peptidylprolyl isomerase F and encoding cyclophilin D (CypD), is a key component of the mitochondrial permeability transition pore (mPTP) in mitochondria. It plays a crucial role in regulating mitochondrial function, such as controlling calcium efflux through mPTP flickering. It is involved in multiple biological processes including cell survival, stress response, and is associated with pathways related to calcium overload, reactive oxygen species (ROS) production, and autophagy [1,2,3].

In a mouse model of lung ischemia-reperfusion (I/R) injury after lung transplantation, PPIF was found to exacerbate the injury by promoting calcium overload-induced neutrophil extracellular traps (NETs) formation. Inhibition of PPIF using its inhibitor cyclosporin A (Cys A) alleviated the calcium overload-induced inflammatory response, ROS content, and NETs formation [1]. In Nynrin-deficient mice, deletion of Nynrin activates Ppif, leading to overexpression of CypD and further mitochondrial dysfunction. Strategies like Ppif haploinsufficiency or pharmacological inhibition of CypD significantly mitigate these effects, restoring hematopoietic stem cell (HSC) function [2].

In conclusion, Ppif is essential for mitochondrial function regulation, with its dysregulation being linked to various disease conditions. Mouse models, especially KO/CKO models, have been instrumental in revealing its role in lung I/R injury and HSC function maintenance, highlighting its potential as a therapeutic target in related diseases.