Pip4k2c, phosphatidylinositol 5-phosphate 4-kinase, type II, gamma, is a lipid kinase involved in phosphoinositide signaling pathways. It has potential scaffolding roles in immune modulation and autophagy-dependent catabolism, and is also associated with the focal adhesion pathway [2,4].

Loss-of-function studies have revealed significant insights. In mice, deletion of Pip4k2c had no impact on lung metastasis or primary tumor growth but conferred liver-metastatic organotropism. Pip4k2c-deficient cells exploited the insulin-rich liver milieu for organ-specific metastasis through insulin-dependent PI3K-AKT pathway activation [1]. In adult Pip4k2c-/-mice, three weeks after transverse aortic constriction (TAC), there were higher rates of cardiac hypertrophy, fibrosis, and sudden death compared to wild-type mice [3]. In WDR73 knockout HEK 293 cells, PIP4K2C protein stability was disrupted, leading to weakened focal adhesion formation, and podocyte-specific conditional knockout (Wdr73 CKO) mice showed podocyte foot process injury and albuminuria [4].

In conclusion, Pip4k2c plays crucial roles in metastasis organotropism, cardiac function, and focal adhesion. Gene knockout and conditional knockout mouse models have been instrumental in uncovering its functions in liver metastasis, cardiac hypertrophy and fibrosis, and nephrotic syndrome related to Galloway-Mowat syndrome. These findings provide potential therapeutic targets for treating related diseases.