Nipsnap1, short for 4-Nitrophenylphosphatase Domain and Non-Neuronal SNAP25-Like 1, is a gene with diverse functions. It localizes to the mitochondrial matrix and is involved in multiple biological pathways such as non-shivering thermogenesis, mitophagy, and cellular senescence regulation. It also plays a role in pain transmission and may be related to inflammatory pain and TRPV6 channel regulation [1,2,3,4,5].

In gene-knockout studies, Nipsnap1 knockout (N1-KO) mice are unable to sustain activated energy expenditure and have lower body temperature during extended cold challenges, indicating its importance in long-term thermogenic maintenance in brown adipose tissue (BAT) [1]. In zebrafish, lack of functional Nipsnap1 leads to reduced mitophagy in the brain and parkinsonian phenotypes [3]. In the context of liver fibrosis, Nipsnap1 overexpression improves mitophagy and attenuates extracellular matrix production, while interference with it disrupts the beneficial effect of SIRT3 on mitophagy and liver fibrosis alleviation [2]. NIPSNAP1-deficient mice show exacerbated inflammatory pain, suggesting its role in the pathogenesis of such pain [4].

In conclusion, Nipsnap1 is crucial for maintaining normal physiological functions. Its functions range from energy metabolism regulation in BAT to mitophagy in different tissues and pain-related processes. The use of gene-knockout models in mice and zebrafish has significantly contributed to understanding its role in diseases like non-shivering thermogenesis-related metabolic disorders, liver fibrosis, and inflammatory pain.