Cds2, short for CDP-diacylglycerol synthetase-2, is a metabolic enzyme that controls phosphoinositide recycling. It converts phosphatidic acid (PA) to CDP-DG, an essential intermediate in the de novo synthesis of phosphatidylinositol (PI) [2,5]. This enzyme is involved in crucial biological processes such as vascular morphogenesis, lipid metabolism, and energy metabolism [1,2,4]. Genetic models, like gene knockout (KO) mouse models, have been instrumental in studying its functions.

In endothelial cells, genetic ablation of Cds2 in zebrafish and mice switches the output of VEGFA signaling from promoting angiogenesis to inducing vessel regression. This occurs due to reduced phosphatidylinositol (4,5)-bisphosphate (PIP2) availability, leading to phosphatidylinositol (3,4,5)-triphosphate (PIP3) deficiency and FOXO1 activation, ultimately suppressing tumor growth [1]. In primary mouse macrophages, Cds2 deficiency leads to increased de novo PA synthesis, while in sustained GPCR-stimulation of PLC, it fails to maintain enhanced PI synthesis via the 'PI cycle' [2]. In liver-specific Cds2-deficient mice, it causes hepatic steatosis, inflammation, and fibrosis due to impaired mitochondrial function and decreased mitochondrial PE levels [3].

In conclusion, Cds2 is essential for normal vascular development, lipid metabolism, and mitochondrial function. The use of KO mouse models has revealed its significance in diseases such as tumor growth regulation and the progression of non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH) and fibrosis. Understanding Cds2 functions provides insights into the underlying mechanisms of these biological processes and diseases.