CPT1C is an enzyme present throughout the nervous system, which is specifically expressed in neurons, showing remarkable amounts in the hypothalamus, hippocampus, cortex, cerebellum and amygdala. Unlike other CPT1 isoforms, which are involved in the transport of fatty acids inside the mitochondria for their subsequent b-oxidation, CPT1C is located in the endoplasmic reticulum (ER), where it regulates ceramide metabolism. Previous studies reported that CPT1C plays an important role in energy homeostasis and control of body weight. Although the molecular mechanisms underlying these functions remain partially unclear, CPT1C involvement in dendritic spine maturation, ER-mediated axonal transport and AMPA receptor synthesis and trafficking have been described. Due to the wide expression of this protein together with the diverse cellular mechanisms attributed, CPT1C might be involved in additional functions in different brain regions that remain unexplored. Here we carried out a systematic characterization of the role of CPT1C at different —molecular, synaptic and behavioral— levels of complexity. First, CPT1C expression pattern in different brain areas was studied by immunohistochemistry in CPT1C Knock-out (KO) mice and wild-type littermate mice. Then, the role of CPT1C in locomotor activity, energy state, anxiety- and depression-like behavior was explored. In addition, CPT1C involvement in different types of learning was investigated studying motor learning, hippocampal-dependent spatial and habituation memory, and associative instrumental learning in vivo, in behaving mice. To correlate hippocampal-dependent memory processes with synaptic plasticity changes, neural activity and dendritic spine maturation in the hippocampus were evaluated in vitro in these animals. Our data showed energy deficits and impaired locomotor activity in CPT1C KO mice. These animals also exhibited deficits in motor and instrumental learning, as well as in spatial and habituation memory. The latter effects could be attributed to an inefficient hippocampal dendritic spine maturation and long-term plasticity impairments observed at the CA3-CA1 synapse. No changes in mood state were found. Together, our results show that CPT1C is needed for learning and memory processes taking place in brain areas that underlie motor, associative, and non-associative learning, as well as confirm the role of CPT1C in hippocampal synaptic plasticity and energy homeostasis.