NIPSNAP3B (nipsnap homolog 3B) is a mitochondrial protein involved in mitochondrial biogenesis and metabolic homeostasis. Mechanistically, NIPSNAP3B functions through the AMPK signaling pathway to enhance mitochondrial biogenesis, characterized by increased ATP content, mitochondrial mass, and expression of key mitochondrial transcription factors (PGC-1α, NRF1, TFAM) 1. Overexpression of NIPSNAP3B reduces lipid accumulation by decreasing triglyceride levels and suppressing adipogenic factors (PPARγ, C/EBPα), effects that are dependent on AMPK activity 1. NIPSNAP3B exhibits disease relevance across multiple conditions. In hypertrophic cardiomyopathy, cardiac NIPSNAP3B expression strongly correlates with cardiac fibrosis severity, particularly in females 2. NIPSNAP3B was identified as a candidate modifier gene influencing penetrance in Leber's hereditary optic neuropathy, a mitochondrial disease 3. In systemic sclerosis, NIPSNAP3B was identified as a novel susceptibility locus through gene-level association analysis 4. Additionally, NIPSNAP3B serves as a potential diagnostic biomarker for atherosclerosis development through mitochondrial dysfunction pathways 5. Bone mineral density variation in postmenopausal women correlates with NIPSNAP3B expression, though the mechanistic basis remains unclear 6. These findings suggest NIPSNAP3B regulates metabolic and mitochondrial responses relevant to fibrotic, metabolic, and autoimmune diseases.