Ppp2r5c, which encodes the regulatory B56γ subunit of protein phosphatase 2A (PP2A), is involved in cell proliferation, differentiation, and transformation. PP2A is a trimeric enzyme that plays a crucial role in regulating various cellular signaling pathways, cell cycle checkpoints, and apoptosis [7].

In multiple disease models, the role of Ppp2r5c has been elucidated. In a murine model of COPD, deficiency of LincR-Ppp2r5c, a related lncRNA, ameliorated emphysema and pulmonary inflammation by regulating IL-1β ubiquitination through PP2A activity [1]. In hepatic metabolism, hepatocyte-specific knockdown of Ppp2r5c in mice improved systemic glucose tolerance and insulin sensitivity but elevated circulating triglyceride levels, indicating its role in coupling hepatic glucose and lipid homeostasis [2]. In a mouse model of pulmonary cryptococcosis, LincR-Ppp2r5c deficiency mitigated the infection by enhancing the fungicidal activity of neutrophils, associated with increased IL-4 levels [3]. In chronic experimental allergic asthma, LincR-Ppp2r5c knockout alleviated airway remodeling by inhibiting epithelial-mesenchymal transition through the PP2A/TGF-β1 signaling pathway [4]. In acute asthma, LincR-Ppp2r5c regulated Ppp2r5c expression and PP2A activity by forming an RNA-DNA triplex with the Ppp2r5c promoter, leading to Th2 polarization [8]. Also, in childhood acute T lymphocytic leukemia, down-regulation of Ppp2r5c gene expression inhibited Molt-4 cell activity, blocked cells in G2 phase, and promoted apoptosis, likely related to the inhibition of the HSP90-GR signaling pathway [5]. In adult acute myeloid leukemia patients with normal cytogenetics, overexpression of Ppp2r5c was an adverse prognostic factor [6]. Additionally, pathogenic de novo variants in Ppp2r5c cause a neurodevelopmental disorder within the Houge-Janssens syndrome spectrum [9].

In conclusion, Ppp2r5c, through its role in PP2A, is essential in multiple biological processes and disease conditions. Studies using gene knockout or knockdown models in mice have been crucial in revealing its functions in areas such as metabolism, inflammation, fungal infection, and airway remodeling, as well as in understanding its implications in leukemia and neurodevelopmental disorders.