Pip4k2c, also known as phosphatidylinositol-5-phosphate 4-kinase, type II, gamma, is a lipid kinase. It is involved in phosphoinositide signaling, which is crucial for many cellular functions such as autophagy, immune regulation, and metabolic control [3,5,7]. It is part of pathways related to autophagic flux regulation, insulin-dependent PI3K-AKT pathway, and is associated with focal adhesion formation [2,4,6].

In gene knockout studies, loss of Pip4k2c in mice conferred liver-metastatic organotropism as Pip4k2c-deficient cells were hypersensitized to insulin-mediated PI3K/AKT signaling, exploiting the insulin-rich liver environment for metastasis [1]. Deletion of Pip4k2c in adult mice led to higher rates of cardiac hypertrophy, fibrosis, and sudden death after transverse aortic constriction (TAC), while transient upregulation of Pip4k2c using modified mRNA improved heart function [4]. Also, germline deletion of Pip4k2c in mice increased inflammation and T-cell activation with age, along with hyperactivation of mTORC1 signaling [7].

In conclusion, Pip4k2c is essential in regulating multiple biological processes including metastasis, cardiac function, and immune response. Gene knockout mouse models have been instrumental in revealing its role in liver metastasis, heart failure-related conditions, and immune system hyperactivation, providing insights into potential therapeutic strategies for these diseases.