CPT1C is a neuron-specific endoplasmic reticulum protein that functions as a metabolic sensor rather than a canonical fatty acid oxidation enzyme 1. Unlike CPT1A and CPT1B, CPT1C exhibits very low or absent carnitine palmitoyltransferase catalytic activity 23. Instead, CPT1C serves as a palmitoyl thioesterase that depalmitoylates GRIA1 to modulate AMPAR trafficking to the neuronal plasma membrane 2. CPT1C binds malonyl-CoA and couples this signal to ceramide regulation, processes essential for dendritic spine maturation and systemic energy homeostasis 4. In the hypothalamus, the malonyl-CoA-CPT1C axis regulates food intake and body weight; CPT1C knockout mice show reduced feeding and weight gain resistance to high-fat diet 5. Beyond its neuronal roles, CPT1C functions as a metabolic regulator in cancer cells by promoting lipid metabolic reprogramming and adaptation to hypoxia and nutrient stress 61. CPT1C expression correlates with poor prognosis in multiple cancers including pancreatic and gastric malignancies, and mediates immunosuppression through IL-6 signaling in cancer-associated fibroblasts 78. Mutations in CPT1C cause spastic paraplegia 73, highlighting its essential role in neuronal function.