ARMC12 (armadillo repeat containing 12) is a mitochondrial peripheral membrane protein with critical roles in male fertility and cancer progression. In spermatogenesis, ARMC12 is essential for mitochondrial sheath formation during spermiogenesis 1. It functions as an adherence factor between mitochondria, interacting with mitochondrial proteins MIC60, VDAC2, VDAC3, and regulatory proteins TBC1D21 and GK2 to enable proper mitochondrial elongation and coiling along the flagellum 1. Biallelic ARMC12 mutations cause asthenozoospermia with multiple midpiece defects including absent mitochondrial sheath, scattered axoneme, and incomplete plasma membrane 2. In cancer, ARMC12 promotes neuroblastoma progression through a distinct mechanism: it physically interacts with retinoblastoma binding protein 4 (RBBP4) to enhance polycomb repressive complex 2 activity, increasing H3K27me3 levels and repressing tumor suppressor genes 3. Recent evidence suggests ARMC12 also functions within MYC-containing liquid condensates to upregulate nucleoporin genes, promoting nuclear pore complex biogenesis and facilitating neuroblastoma invasion and metastasis 4. Both elevated ARMC12 expression and germline mutations associate with unfavorable clinical outcomes in respective disease contexts 3, 2.