ISOC2 (isochorismatase domain containing 2) is a novel protein containing an isochorismatase domain that localizes to multiple cellular compartments including the cytoplasm, cytosol, mitochondrion, and nucleus 1. The primary function of ISOC2 involves protein-protein interactions, specifically binding and interacting with the tumor suppressor p16(INK4a) 1. Over-expressed ISOC2 inhibits p16(INK4a) expression in a dose-dependent manner, suggesting a role in negative regulation of this tumor suppressor 1. ISOC2 also serves as a direct target of SAHA, a histone deacetylase inhibitor used in cancer therapy 2. At the mitochondrial level, ISOC2 is involved in mitochondrial structure maintenance and is significantly underexpressed in infertile men with varicocele, correlating with impaired mitochondrial function and oxidative stress 3. ISOC2 has clinical relevance to multiple diseases: it was identified as a prognostic mitochondrial-related gene in breast cancer, with expression levels correlating with patient outcomes and immunotherapy response 4. Additionally, a coding region variant in ISOC2 (rs4801638) showed nominal association with neural tube defects in a folate-interaction study 5, and differential splicing of ISOC2 exon 3 was validated in hepatocellular carcinoma samples 6. These findings suggest ISOC2 plays multifaceted roles in cancer development, mitochondrial homeostasis, and developmental anomalies.