NIPSNAP1 (nipsnap homolog 1) is a mitochondrial matrix protein that functions as a primary 'eat me' signal for selective autophagy of damaged mitochondria (mitophagy) 1. Upon mitochondrial depolarization, NIPSNAP1 accumulates on the mitochondrial outer membrane and recruits autophagy machinery including receptors (NDP52, NBR1, p62, TAX1BP1, WDFY3) and ATG8 family proteins to facilitate mitochondrial clearance 1. This process is essential for cellular homeostasis; zebrafish lacking Nipsnap1 display impaired brain mitophagy, dopaminergic neuron loss, reduced motor activity, and increased oxidative stress, resulting in parkinsonian phenotypes 1. Beyond mitophagy, NIPSNAP1 plays broader roles in cellular stress responses. In cancer cells, NIPSNAP1 promotes proliferation and prevents senescence through dual mechanisms: maintaining c-Myc protein stability by sequestering E3 ligase FBXL14, and regulating reactive oxygen species by promoting SIRT3-SOD2 interactions 2. In hepatic ischemia-reperfusion injury, NIPSNAP1 protects against damage by promoting mitophagy and maintaining mitochondrial homeostasis, with its expression regulated by m6A methylation through the IGF2BP2 reader protein 3. Additionally, NIPSNAP1 participates in pain regulation following nocistatin binding in the spinal cord 4. Recent evidence reveals UBE4B-mediated NIPSNAP1 ubiquitination enhances its interaction with autophagy adaptors, enabling Parkin-independent mitophagy 5.