Ppia, also known as peptidylprolyl isomerase A or cyclophilin A, is a central enzyme involved in protein folding. It catalyzes the cis-trans isomerization of proline residues in proteins, which is crucial for protein maturation, assembly, and function [4]. Ppia is also implicated in multiple biological pathways and has been associated with various diseases, highlighting its overall biological importance. Genetic models, such as KO mouse models, have been invaluable in studying Ppia's functions.

In lung cancer, PPIA is required for NRF2 protein stability. Ablation of PPIA in NSCLC cells promotes NRF2 protein degradation and blocks NRF2-driven growth, suggesting its role in cancer progression [1]. In adipogenesis, PPIA-/-mice have less fat and smaller adipocytes compared to wild-type mice. Silencing PPIA in 3T3L1 cells and MEFs from PPIA-/-mice impairs adipocyte differentiation, indicating its importance in obesity [2]. In oral cancer, reducing PPIA expression and secretion significantly decreases cell invasion and migration, suggesting PPIA as a potential therapeutic target [3].

In conclusion, Ppia plays essential roles in protein folding and is involved in biological processes such as adipogenesis and cancer progression. Studies using Ppia KO mouse models have revealed its functions in specific disease areas, including lung, oral cancers, and obesity, providing valuable insights into disease mechanisms and potential therapeutic targets.

References:

1. Lu, Weiqiang, Cui, Jiayan, Wang, Wanyan, Ji, Hongbin, Huang, Jin. 2024. PPIA dictates NRF2 stability to promote lung cancer progression. In Nature communications, 15, 4703. doi:10.1038/s41467-024-48364-4. https://pubmed.ncbi.nlm.nih.gov/38830868/

2. Zhang, Lihong, Li, Zhen, Zhang, Bo, He, Haiyang, Bai, Yun. 2015. PPIA is a novel adipogenic factor implicated in obesity. In Obesity (Silver Spring, Md.), 23, 2093-100. doi:10.1002/oby.21208. https://pubmed.ncbi.nlm.nih.gov/26347493/

3. Liao, En-Chi, Law, Ching-Hsuan, Chen, Hsin-Yi, Chou, Hsiu-Chuan, Chan, Hong-Lin. 2025. PPIA enhances cell growth and metastasis through CD147 in oral cancer. In Archives of biochemistry and biophysics, 765, 110328. doi:10.1016/j.abb.2025.110328. https://pubmed.ncbi.nlm.nih.gov/39921142/

4. Trémillon, Nicolas, Morello, Eric, Llull, Daniel, Ginisty, Hervé, Poquet, Isabelle. 2012. PpiA, a surface PPIase of the cyclophilin family in Lactococcus lactis. In PloS one, 7, e33516. doi:10.1371/journal.pone.0033516. https://pubmed.ncbi.nlm.nih.gov/22442694/