Cpt1a, short for carnitine palmitoyltransferase 1A, is a key rate-limiting enzyme in mitochondrial fatty acid oxidation (FAO) pathway [1,2]. This pathway is essential for energy homeostasis during fasting or prolonged exercise, especially in tissues with high energy demands. The conversion of acyl-coenzyme As into acyl-carnitines by Cpt1a is the rate-limiting step, enabling fatty acids to cross membranes and enter mitochondria for oxidation [1].

In various disease conditions, Cpt1a has been shown to play significant roles. In lung cancer, targeting Cpt1a induces ferroptosis and synergizes with immunotherapy. Cpt1a acts with L-carnitine from tumor-associated macrophages to drive ferroptosis-resistance and CD8+ T cells inactivation [3]. In nasopharyngeal carcinoma, the active FAO with up-regulated Cpt1a confers radiation resistance, and inhibiting Cpt1a re-sensitizes cells to radiation therapy [5]. In colorectal and esophageal squamous cell carcinomas, Cpt1a-mediated FAO promotes metastasis by inhibiting anoikis [6,8]. Also, in sepsis, mitochondrial STAT3 exacerbates the condition by driving Cpt1a-mediated FAO [4]. On the contrary, in chronic kidney disease, overexpression of Cpt1a in renal tubule protects from kidney fibrosis by restoring mitochondrial homeostasis [7].

In conclusion, Cpt1a is crucial for the FAO pathway and energy metabolism. Studies, especially those using gene-knockout or conditional-knockout mouse models in various disease areas such as cancer, sepsis, and kidney disease, have revealed its diverse roles. These findings provide potential therapeutic targets for treating related diseases by modulating Cpt1a-mediated processes.