Pla2g4a, also known as phospholipase A2, group IVA (cytosolic, calcium-dependent) [2], is involved in lipid metabolism-related pathways. It can regulate the metabolism of glycerophospholipids, and its activity is related to many biological processes and disease conditions [3]. Genetic models such as KO/CKO mouse models are valuable for studying its functions.

In cerebral ischemia-reperfusion injury, inhibition of the neuronal PTRF/Pla2g4a-axis in mice reduced neurological deficits, cerebral infarct volumes, and mortality rates, suggesting that the STAT3/HIF-1α/PTRF-axis, which regulates the activity and stability of Pla2g4a, exacerbates the injury [1]. In traumatic brain injury, in vivo pharmacological inhibition of Pla2g4a attenuated TBI-induced lysosomal membrane permeabilization, autophagy impairment, and neuronal loss, improving neurological outcomes [2]. In platinum-resistant gastric cancer, Pla2g4a and ACHE regulated the endogenous lipid profile through the glycerophospholipid metabolism pathway [3]. In hepatocellular carcinoma, Lnc-Pla2g4a-4 promotes HCC progression by targeting the miR-23b-3p/versican axis [4]. In acute myeloid leukemia, high Pla2g4a expression is associated with shorter overall survival in non-M3/NPM1 wildtype patients [5]. In valproic acid-induced hepatotoxicity, inhibition of Pla2g4a attenuated lysosomal membrane permeabilization and restored impaired autophagic flux [6].

In conclusion, Pla2g4a is crucial in lipid-related metabolic pathways and plays significant roles in multiple disease conditions including ischemic stroke, traumatic brain injury, cancer, and drug-induced hepatotoxicity. The study of Pla2g4a using KO/CKO mouse models has provided insights into its functions in these diseases, facilitating a better understanding of disease mechanisms and potentially guiding the development of new therapeutic strategies.