The molecular activation of non-shivering thermogenesis (NST) has strong potential to combat obesity and metabolic disease. However, the current approaches to activate NST are limited due to its safety and feasibility concerns as well as its temporal nature. Understanding the mechanism of how NST is maintained, once activated, will contribute to minimizing the potential risk and complexity of current anti-obesity treatments. Here, I present 4-Nitrophenylphosphatase Domain and Non-Neuronal SNAP25-Like 1 (Nipsnap1) as a critical regulator of long-term thermogenic maintenance in brown adipose tissue (BAT). Nipsnap1 localizes within mitochondria and increases its transcript and protein levels in response to chronic cold and _3 adrenergic signaling. BAT-specific Nipsnap1 knockout mice (N1-KO) were unable to sustain activated energy expenditure and failed to protect their body temperature in the face of an extended cold challenge. Furthermore, when exposed to the pharmacological _3 agonist CL 316, 243, the N1-KO mice exhibit significant hyperphagia and altered energy balance. Mechanistically, I demonstrate that Nipsnap1 integrates with lipid metabolism and BAT-specific ablation of Nipsnap1 leads to severe defects in beta-oxidation capacity when exposed to a cold environmental challenge. My findings identify Nipsnap1 as a potent regulator of long-term NST maintenance.