NIPSNAP2 (nipsnap homolog 2) functions as a mitochondrial 'eat me' signal that facilitates mitophagy, the selective autophagy of damaged mitochondria. Upon mitochondrial depolarization, NIPSNAP2 accumulates on the mitochondrial outer membrane and recruits key autophagy machinery, including autophagy receptors (CALCOCO2/NDP52, NBR1, SQSTM1/p62, TAX1BP1, and WDFY3/ALFY) and ATG8 family proteins (MAP1LC3A, MAP1LC3B, MAP1LC3C, GABARAP, GABARAPL1, and GABARAPL2) 1. NIPSNAP2 works redundantly with NIPSNAP1 to ensure sustained recruitment of SQSTM1-like receptors for efficient mitophagy 2. The protein localizes to the mitochondrial inner membrane space and requires HSP60 for proper folding and stability 3. In skeletal muscle of older adults, NIPSNAP2 expression positively correlates with physical performance, muscle volume, and mitochondrial function, suggesting its importance in age-related muscle health 4. NIPSNAP2 has also been identified as a candidate susceptibility gene for cataract development through transcriptome-wide association studies 5. As a member of an evolutionarily conserved gene family, NIPSNAP2 represents a critical component of mitochondrial quality control mechanisms essential for cellular homeostasis.