AGK, also known as acylglycerol kinase, is a mitochondrial membrane kinase that catalyzes the formation of phosphatidic acid and lysophosphatidic acid. It is a subunit of the translocase of the mitochondrial inner membrane 22 (TIM22) protein import complex and is involved in multiple biological pathways, including mitochondrial fatty acid metabolism, the PI3K-AKT-mTOR signaling pathway, and the Mpl/Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (Stat3) pathway. Mutations in AGK are the leading cause of Sengers syndrome, highlighting its biological importance in human health [1,2,3,4]. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, are valuable for studying AGK's function.

Hepatic-specific AGK-deficient mice developed severe liver damage, lipid accumulation, and spontaneously developed NASH with age. This indicates that AGK plays a crucial role in maintaining mitochondrial integrity and preventing the progression of NASH, likely by interacting with mitochondrial respiratory chain complex I subunits [1]. Megakaryocyte/platelet-specific AGK-deficient mice developed thrombocytopenia and splenomegaly, mainly due to inefficient bone marrow thrombocytopoiesis and excessive extramedullary hematopoiesis, revealing AGK's importance in megakaryocyte differentiation and platelet biogenesis [4].

In conclusion, AGK is essential for maintaining mitochondrial function, as demonstrated by its role in NASH prevention through interactions with mitochondrial respiratory chain complex I. It also plays a critical role in thrombocytopoiesis. The use of AGK KO/CKO mouse models has provided valuable insights into these functions, which are relevant to understanding Sengers syndrome, NASH, and platelet-related disorders [1,2,3,4].